Sartaj Tabassum - Academia.edu (original) (raw)

Papers by Sartaj Tabassum

Research paper thumbnail of Chiral nano heterobimetallic DNA receptors: In vitro binding studies, cleavage activity and DNA condensation studies (TEM and AFM imaging)

Journal of Organometallic Chemistry, 2012

A new chiral nano heterobimetallic CoeSn and ZneSn complexes were designed and thoroughly charact... more A new chiral nano heterobimetallic CoeSn and ZneSn complexes were designed and thoroughly characterized by various spectroscopic viz 1 H, 13 C, 119 Sn NMR, ESI-MS, magnetic moment, analytical and visualization techniques. The electronic absorption and spectroscopic data reveal that the Co(II) ion exhibits a square pyramidal geometry. 119 Sn NMR spectral data and powered XRD measurements support the hexa-coordinated geometry of the Sn(IV) atom. The binding studies of the heterobimetallic CoeSn complex with CT-DNA were carried out by using various biophysical techniques viz UVevis absorption, emission spectroscopy and cyclic voltammetric measurements, recommended predominantly electrostatic mode of interaction of the complex with CT-DNA. The gel electrophoretic patterns of supercoiled pBR322 DNA with varying concentration of the CoeSn complex exhibit an ability to cleave DNA and follow hydrolytic pathway mechanism. Furthermore, the application of chiral nano heterobimetallic CoeSn complex as DNA gene transporter was evaluated by DNA condensation and ascertained by employing the visualization techniques i.e. TEM and AFM, which illustrated that the CoeSn complex induces the condensation of CT-DNA to a particulate nanostructure.

Research paper thumbnail of Synthesis and crystal structure determination of copper(II)-complex: In vitro DNA and HSA binding, pBR322 plasmid cleavage, cell imaging and cytotoxic studies

European Journal of Medicinal Chemistry, 2014

New Cu(II) complex 1 of indole-3-propionic acid and 1,10-phenanthroline was synthesized and chara... more New Cu(II) complex 1 of indole-3-propionic acid and 1,10-phenanthroline was synthesized and characterized by analytical, spectroscopic and single crystal X-ray diffraction. In vitro DNA binding studies of 1 was performed by employing UV-vis and fluorescence spectroscopic techniques. The binding affinity towards human serum albumin (HSA) was also investigated to understand the carrier role in body system, as the time dependent HPLC experiment of 1 revealed that bonded drug with protein releases slowly in presence of DNA. Complex 1 exhibited good anti-tumor activity (GI50 values <10 μg/ml), and to elucidate the mechanism of tumor inhibition, topoisomerase I enzymatic activity was carried out and further validated by cell imaging studies which clearly showed its nuclear localization.

Research paper thumbnail of Coumarin centered copper(ii) complex with appended-imidazole as cancer chemotherapeutic agents against lung cancer: molecular insight via DFT-based vibrational analysis

RSC Adv.

Synthesis and structural characterization of the novel copper complex, DFT based vibrational anal... more Synthesis and structural characterization of the novel copper complex, DFT based vibrational analysis, DNA binding studies. In vitro cytotoxicity against A549 cancer cell lines and estimation of GSH, ROS, LPO levels, have been reported.

Research paper thumbnail of Loss of DUSP3 activity radiosensitizes human tumor cell lines via attenuation of DNA repair pathways

Biochimica et biophysica acta, Jul 4, 2017

Radiotherapy causes the regression of many human tumors by increasing DNA damage, and the novel m... more Radiotherapy causes the regression of many human tumors by increasing DNA damage, and the novel molecular mechanisms underlying the genomic instability leading to cancer progression and metastasis must be elucidated. Atypical dual-specificity phosphatase 3 (DUSP3) has been shown to down-regulate mitogen-activated protein kinases (MAPKs) to control the proliferation and apoptosis of human cancer cells. We have recently identified novel molecular targets of DUSP3 that function in DNA damage response and repair; however, whether DUSP3 affects these processes remains unknown. Tumor cell lines in which DUSP3 activity was suppressed by pharmacological inhibitors or a targeted siRNA were exposed to gamma radiation, and proliferation, survival, DNA strand breaks and recombination repair pathways were sequentially analyzed. The combination of reduced DUSP3 activity and gamma irradiation resulted in decreased cellular proliferation and survival and increased cellular senescence compared with ...

Research paper thumbnail of p53-Dependent Apoptotic Mechanism of a New Designer Bimetallic Compound Tri-phenyl Tin Benzimidazolethiol Copper Chloride (TPT-CuCl2): In Vivo Studies in Wistar Rats as Well as in Vitro Studies in Human Cervical Cancer Cells

Journal of Pharmacology and Experimental Therapeutics, 2004

We have studied the effect of tri-phenyl tin benzimadazolethiolcopper chloride (TPT-CuCl(2)), a n... more We have studied the effect of tri-phenyl tin benzimadazolethiolcopper chloride (TPT-CuCl(2)), a novel bimetallic compound, on the regulation of apoptosis in HeLa cells, MCF-7 cells, and in vivo Wistar rat model. TPT-CuCl(2) induces significant apoptosis in HeLa cell line characterized by DNA fragmentation and chromosome condensation. Comet assay revealed that TPT-CuCl(2) targets and causes severe damage to the DNA. Treatment of HeLa cells with TPT-CuCl(2) rescues the accumulation of p53 from the suppression of human papilloma virus E6, resulting in a dramatic up-regulation of Bax and Bak and down-regulation of the antiapoptotic factor Survivin. Apoptotic induction by TPT-CuCl(2) was shown to mediate in a p53-depedent manner; loss of p53 impairs the release of cytochrome c and Smac/DIABLO from mitochondria to cytosol. Moreover, we have shown that TPT-CuCl(2) induced-apoptosis was through an intrinsic mitochondrial pathway, which was inhibited by viral oncoprotein E1B19K. Caspase-3 was found to be indispensable in TPT-CuCl(2)-triggered apoptosis signaling pathway, because caspase-3 deficient cell line MCF-7 was resistant to TPT-CuCl(2). Furthermore, in vivo studies using C6 glioblastoma xenograft rat model revealed that TPT-CuCl(2) exhibits significant antiproliferative activity against tumor development with minimal cytotoxicity toward normal physiological function of the experimental rats. These findings imply the attractiveness of TPT-CuCl(2) as a drug candidate for further development.

Research paper thumbnail of Elucidating the Interaction of Enantiomeric Cu(Ii) Complexes with DNA, Rna and Hsa: A Comparative Study

Research paper thumbnail of Synthesis, Characterization, and Kinetics of Mono- and Heterobimetallic Complexes of Bis(5-nitroindazolyl) Methane Towards CTDNA

Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry

A new ligand bis(5-nitroindazolyl) methane has been synthesized and characterized by the elementa... more A new ligand bis(5-nitroindazolyl) methane has been synthesized and characterized by the elemental analysis, I.R., H, andC n.m.r. spectroscopy. A series of transition metal complexes have been prepared and new bimetallic complexes of CuII and CoII with organotin(IV) were also synthesized. All complexes have been characterized by various physico-chemical methods. The reaction kinetics of monometallic (C30H20N14O14Cu) and the bimetallic complexes

Research paper thumbnail of Recent advances in metallodrug-like molecules targeting non-coding RNAs in cancer chemotherapy

Coordination Chemistry Reviews

Research paper thumbnail of Cadmium-induced neurodegeneration and activation of noncanonical sonic hedgehog pathway in rat cerebellum

Journal of Biochemical and Molecular Toxicology

Cadmium is a nonessential toxic heavy metal, which enters the body easily and damages the cellula... more Cadmium is a nonessential toxic heavy metal, which enters the body easily and damages the cellular system. The sonic hedgehog (Shh) signaling pathway is one of the key regulatory pathways, which define neural growth and development. This study aimed to explore how cadmium exposure affects neural activities, Shh signaling cascade, and its downstream target genes. Total 18 male Wistar rats were randomly divided into two groups, control and test groups. Test rats were administered with 3 mg cadmium/kg body weight, while the control rats were treated with vehicle continuously for 28 days. Thereafter, rats were killed and the isolated brain samples were examined using oxidative stress assessment, histological and immunohistological behavioral assessment, polymerase chain reaction (PCR), and the comet assay. A disturbed oxidative balance, DNA damage, and an upregulated Shh signaling pathway were observed in cadmium-treated samples. Loss of structural integrity in cerebellum and loss of motor activity were observed in cadmium-treated rats.

Research paper thumbnail of A zwitterionic Zn(II) benzothiazole nanohybrid conjugate as hydrolytic DNA cleavage agent

Inorganic Chemistry Communications

Research paper thumbnail of {"__content__"=>"-Carboline Silver Compound Binding Studies with Human Serum Albumin: A Comprehensive Multispectroscopic Analysis and Molecular Modeling Study.", "i"=>{"__content__"=>"β"}}

Bioinorganic chemistry and applications, 2018

β-Carbolines (βCs) belong to the naturally occurring alkaloid family, derived from 9H-pyrido[3,4-... more β-Carbolines (βCs) belong to the naturally occurring alkaloid family, derived from 9H-pyrido[3,4-b]indole, also known as norharmane (Hnor). Knowing the importance of the βCs alkaloid family in biological processes, a comprehensive binding study is reported of four Ag(I) compounds containing the ligand Hnor and having different counteranions, namely, NO 3 − , ClO 4 − , BF 4 − , and PF 6 − , with human serum albumin (HSA) as a model protein. Different approaches like UV-visible, fluorescence spectroscopy, circular dichroism (CD), and molecular docking studies have been used for this purpose. e fluorescence results establish that the phenomenon of binding of Ag(Hnor) complexes to HSA can be deduced from the static quenching mechanism. e results showed a significant binding propensity of the used Ag(I) compounds towards HSA. e role of the counteranion on the binding of Ag(I) compounds to HSA appeared to be remarkable. Compounds with (ClO 4 −) and (NO 3 −) were found to have the most efficient binding towards HSA as compared to BF 4 − and PF 6 −. Circular dichroism (CD) studies made clear that conformational changes in the secondary structure of HSA were induced by the presence of Ag(I) compounds. Also, the α-helical structure of HSA was found to get transformed into a β-sheeted structure. Interestingly, (ClO 4 −) and (NO 3 −) compounds were found to induce most substantial changes in the secondary structure of HSA. e outcome of this study may contribute to understanding the propensity of proteins involved in neurological diseases (such as Alzheimer's and Parkinson's diseases) to undergo a similar transition in the presence of Ag-β-carboline compounds.

Research paper thumbnail of Loss of DUSP3 activity radiosensitizes human tumor cell lines via attenuation of DNA repair pathways

Biochimica et biophysica acta, Jul 4, 2017

Radiotherapy causes the regression of many human tumors by increasing DNA damage, and the novel m... more Radiotherapy causes the regression of many human tumors by increasing DNA damage, and the novel molecular mechanisms underlying the genomic instability leading to cancer progression and metastasis must be elucidated. Atypical dual-specificity phosphatase 3 (DUSP3) has been shown to down-regulate mitogen-activated protein kinases (MAPKs) to control the proliferation and apoptosis of human cancer cells. We have recently identified novel molecular targets of DUSP3 that function in DNA damage response and repair; however, whether DUSP3 affects these processes remains unknown. Tumor cell lines in which DUSP3 activity was suppressed by pharmacological inhibitors or a targeted siRNA were exposed to gamma radiation, and proliferation, survival, DNA strand breaks and recombination repair pathways were sequentially analyzed. The combination of reduced DUSP3 activity and gamma irradiation resulted in decreased cellular proliferation and survival and increased cellular senescence compared with ...

Research paper thumbnail of Heteroleptic Copper(I) Complexes of “Scorpionate” Bis-pyrazolyl Carboxylate Ligand with Auxiliary Phosphine as Potential Anticancer Agents: An Insight into Cytotoxic Mode

Scientific Reports, 2017

New copper(I) complexes [CuCl(PPh 3)(L)] (1: L = L A = 4-carboxyphenyl)bis(3,5-dimethylpyrazolyl)... more New copper(I) complexes [CuCl(PPh 3)(L)] (1: L = L A = 4-carboxyphenyl)bis(3,5-dimethylpyrazolyl) methane; (2: L = L B = 3-carboxyphenyl)bis(3,5-dimethylpyrazolyl)methane) were prepared and characterised by elemental analysis and various spectroscopic techniques such as FT-IR, NMR, UV-Vis, and ESI-MS. The molecular structures of complexes 1 and 2 were analyzed by theoretical B3LYP/DFT method. Furthermore, in vitro DNA binding studies were carried out to check the ability of complexes 1 and 2 to interact with native calf thymus DNA (CT-DNA) using absorption titration, fluorescence quenching and circular dichroism, which is indicative of more avid binding of the complex 1. Moreover, DNA mobility assay was also conducted to study the concentration-dependent cleavage pattern of pBR322 DNA by complex 1, and the role of ROS species to have a mechanistic insight on the cleavage pattern, which ascertained substantial roles by both hydrolytic and oxidative pathways. Additionally, we analyzed the potential of the interaction of complex 1 with DNA and enzyme (Topo I and II) with the aid of molecular modeling. Furthermore, cytotoxic activity of complex 1 was tested against HepG2 cancer cell lines. Thus, the potential of the complex 1 is promising though further in vivo investigations may be required before subjecting it to clinical trials. Cancer is ranked the second most common cause of death, only after cardiovascular diseases. Hepatocellular carcinoma or hepatic/liver cancer is the sixth most widespread cancer and the third leading cause of cancer-associated deaths 1. In the year 2016, in the USA alone, new cases and deaths due to liver/intrahepatic bile duct cancer were found to be 39230 (incidence) and 27170 (mortality) 2. Several research efforts have been made to deal with liver cancer, which include the area of metal-based drugs for cancer chemotherapy. The field of metallodrugs came to be recognized after the foundation laid by the serendipitous discovery of cisplatin (cis-diamminedichloroplatinum(II)). Cisplatin exhibited wide applications as a chemotherapeutic agent, but it has also been found to produce severe side effects 3-9. Since then there has been a hectic search for better metal-based cancer chemotherapeutic drugs. The unique properties of metal ions can be taken to advantage in

Research paper thumbnail of Synthesis of carbohydrate-conjugate heterobimetallic CuII-SnIV2 and ZnII-SnIV2 complexes; their interactions with CT DNA and nucleotides; DNA cleavage, in-vitro cytotoxicity

European Journal of Medicinal Chemistry, 2010

The new heterobimetallic Ni II eSn 2 IV (1), Cu II eSn 2 IV (2) and Zn II eSn 2 IV (3) complexes,... more The new heterobimetallic Ni II eSn 2 IV (1), Cu II eSn 2 IV (2) and Zn II eSn 2 IV (3) complexes, containing D-glucosamine, 1,8-diamino-3,6-diazaoctane and imidazole were isolated and characterized by spectral and analytical methods. The proposed geometry of Ni(II) and Cu(II) in 1 and 2 was square pyramidal, Zn (II) in 3 exhibited tetrahedral while Sn(IV) exhibits hexacoordinate environment, respectively. The X-ray powder diffraction (XRPD) confirmed the amorphous nature of all the complexes. The interaction studies of 2 and 3 with CT DNA were carried out by various biophysical techniques to show the mode of binding. The interaction of 2 and 3 with nucleotides viz 5 0-GMP and 5 0-TMP, respectively were further confirmed by 1 H, 31 P and 119 Sn NMR spectroscopy. The complex 2 exhibited effective cleavage activity with pBR322 DNA. Furthermore, the cytotoxicity of 2 was examined on a panel of human tumor cell lines of different histological origins and showed good activity against Colo205 and A2780 (GI50 < 10 mg/ml).

Research paper thumbnail of Synthesis and crystal structure elucidation of new copper(II)-based chemotherapeutic agent coupled with 1,2-DACH and orthovaniline: Validated by in vitro DNA/HSA binding profile and pBR322 cleavage pathway

Journal of photochemistry and photobiology. B, Biology, Jan 2, 2016

New copper(II)-based complex (1) was synthesized and characterized by analytical, spectroscopic a... more New copper(II)-based complex (1) was synthesized and characterized by analytical, spectroscopic and single crystal X-ray diffraction. The in vitro binding studies of complex 1 with CT DNA and HSA have been investigated by employing biophysical techniques to examine the binding propensity of 1 towards DNA and HSA. The results showed that 1 avidly binds to CT DNA via electrostatic mode along with the hydrogen bonding interaction of NH2 and CN groups of Schiff base ligand with the base pairs of DNA helix, leads to partial unwinding and destabilization of the DNA double helix. Moreover, the CD spectral studies revealed that complex 1 binds through groove binding interaction that stabilizes the right-handed B-form of DNA. Complex 1 showed an impressive photoinduced nuclease activity generating single-strand breaks in comparison with the DNA cleavage activity in presence of visible light. The mechanistic investigation revealed the efficiency of 1 to cleave DNA strands by involving the gen...

Research paper thumbnail of A Chloro-Bridged Heterobimetallic (η6-Arene)ruthenium–Organotin Complex as an Efficient Topoisomerase Iα Inhibitor

Organometallics, Apr 18, 2013

ABSTRACT The chloro-bridged heterobimetallic complex (η6-hexamethylbenzene)Ru(dmp)(μ-Cl)2Sn(CH3)2... more ABSTRACT The chloro-bridged heterobimetallic complex (η6-hexamethylbenzene)Ru(dmp)(μ-Cl)2Sn(CH3)2Cl2 was designed, synthesized, and characterized by various spectroscopic methods, viz. IR, 1H and 13C NMR, and ESI MS, and single-crystal X-ray crystallography as an approach toward multitargeting metal-based potential anticancer drug candidates. In vitro DNA binding studies confirmed the binding affinity of the complex toward the minor groove of DNA, which is further validated by docking studies. Furthermore, the complex exhibited significant inhibitory effects on topoisomerase Iα at a very low concentration (8 μM). The cytotoxicity of the complex against HeLa and HepG2 cancer cell lines was evaluated, which revealed significant regression in cancerous cells in comparison with the standard drug.

Research paper thumbnail of Synthesis, characterization, solution stability studies, electrochemistry, and DNA-binding behavior of Cu(II) complexes of D-gluconic acid

Journal of Carbohydrate Chemistry, Nov 1, 2005

Research paper thumbnail of Synthesis and characterization of Co( ii ) and Fe( ii ) peptide conjugates as hydrolytic cleaving agents and their preferential enantiomeric disposition for CT-DNA: structural investigation of l -enantiomers by DFT and molecular docking studies

RSC Adv., 2015

Molecular docked model of Co(ii) peptide conjugate with DNA and the mechanism of hydrolytic cleav... more Molecular docked model of Co(ii) peptide conjugate with DNA and the mechanism of hydrolytic cleavage of pBR322 DNA.

Research paper thumbnail of Investigation of diorganotin(IV) complexes: Synthesis, characterization, in vitro DNA binding studies and cytotoxicity assessment of di-n-butyltin(IV) complex

Inorganica Chimica Acta, 2014

Research paper thumbnail of Synthesis and spectroscopic characterization of diorganotin( iv ) complexes of N′-(4-hydroxypent-3-en-2-ylidene)isonicotinohydrazide: chemotherapeutic potential validation by in vitro interaction studies with DNA/HSA, DFT, molecular docking and cytotoxic activity

RSC Adv., 2015

A diorganotin(iv) hydrazide complex as a potential cancer chemotherapeutic agent targeting DNA us... more A diorganotin(iv) hydrazide complex as a potential cancer chemotherapeutic agent targeting DNA using the carrier protein HSA.

Research paper thumbnail of Chiral nano heterobimetallic DNA receptors: In vitro binding studies, cleavage activity and DNA condensation studies (TEM and AFM imaging)

Journal of Organometallic Chemistry, 2012

A new chiral nano heterobimetallic CoeSn and ZneSn complexes were designed and thoroughly charact... more A new chiral nano heterobimetallic CoeSn and ZneSn complexes were designed and thoroughly characterized by various spectroscopic viz 1 H, 13 C, 119 Sn NMR, ESI-MS, magnetic moment, analytical and visualization techniques. The electronic absorption and spectroscopic data reveal that the Co(II) ion exhibits a square pyramidal geometry. 119 Sn NMR spectral data and powered XRD measurements support the hexa-coordinated geometry of the Sn(IV) atom. The binding studies of the heterobimetallic CoeSn complex with CT-DNA were carried out by using various biophysical techniques viz UVevis absorption, emission spectroscopy and cyclic voltammetric measurements, recommended predominantly electrostatic mode of interaction of the complex with CT-DNA. The gel electrophoretic patterns of supercoiled pBR322 DNA with varying concentration of the CoeSn complex exhibit an ability to cleave DNA and follow hydrolytic pathway mechanism. Furthermore, the application of chiral nano heterobimetallic CoeSn complex as DNA gene transporter was evaluated by DNA condensation and ascertained by employing the visualization techniques i.e. TEM and AFM, which illustrated that the CoeSn complex induces the condensation of CT-DNA to a particulate nanostructure.

Research paper thumbnail of Synthesis and crystal structure determination of copper(II)-complex: In vitro DNA and HSA binding, pBR322 plasmid cleavage, cell imaging and cytotoxic studies

European Journal of Medicinal Chemistry, 2014

New Cu(II) complex 1 of indole-3-propionic acid and 1,10-phenanthroline was synthesized and chara... more New Cu(II) complex 1 of indole-3-propionic acid and 1,10-phenanthroline was synthesized and characterized by analytical, spectroscopic and single crystal X-ray diffraction. In vitro DNA binding studies of 1 was performed by employing UV-vis and fluorescence spectroscopic techniques. The binding affinity towards human serum albumin (HSA) was also investigated to understand the carrier role in body system, as the time dependent HPLC experiment of 1 revealed that bonded drug with protein releases slowly in presence of DNA. Complex 1 exhibited good anti-tumor activity (GI50 values &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10 μg/ml), and to elucidate the mechanism of tumor inhibition, topoisomerase I enzymatic activity was carried out and further validated by cell imaging studies which clearly showed its nuclear localization.

Research paper thumbnail of Coumarin centered copper(ii) complex with appended-imidazole as cancer chemotherapeutic agents against lung cancer: molecular insight via DFT-based vibrational analysis

RSC Adv.

Synthesis and structural characterization of the novel copper complex, DFT based vibrational anal... more Synthesis and structural characterization of the novel copper complex, DFT based vibrational analysis, DNA binding studies. In vitro cytotoxicity against A549 cancer cell lines and estimation of GSH, ROS, LPO levels, have been reported.

Research paper thumbnail of Loss of DUSP3 activity radiosensitizes human tumor cell lines via attenuation of DNA repair pathways

Biochimica et biophysica acta, Jul 4, 2017

Radiotherapy causes the regression of many human tumors by increasing DNA damage, and the novel m... more Radiotherapy causes the regression of many human tumors by increasing DNA damage, and the novel molecular mechanisms underlying the genomic instability leading to cancer progression and metastasis must be elucidated. Atypical dual-specificity phosphatase 3 (DUSP3) has been shown to down-regulate mitogen-activated protein kinases (MAPKs) to control the proliferation and apoptosis of human cancer cells. We have recently identified novel molecular targets of DUSP3 that function in DNA damage response and repair; however, whether DUSP3 affects these processes remains unknown. Tumor cell lines in which DUSP3 activity was suppressed by pharmacological inhibitors or a targeted siRNA were exposed to gamma radiation, and proliferation, survival, DNA strand breaks and recombination repair pathways were sequentially analyzed. The combination of reduced DUSP3 activity and gamma irradiation resulted in decreased cellular proliferation and survival and increased cellular senescence compared with ...

Research paper thumbnail of p53-Dependent Apoptotic Mechanism of a New Designer Bimetallic Compound Tri-phenyl Tin Benzimidazolethiol Copper Chloride (TPT-CuCl2): In Vivo Studies in Wistar Rats as Well as in Vitro Studies in Human Cervical Cancer Cells

Journal of Pharmacology and Experimental Therapeutics, 2004

We have studied the effect of tri-phenyl tin benzimadazolethiolcopper chloride (TPT-CuCl(2)), a n... more We have studied the effect of tri-phenyl tin benzimadazolethiolcopper chloride (TPT-CuCl(2)), a novel bimetallic compound, on the regulation of apoptosis in HeLa cells, MCF-7 cells, and in vivo Wistar rat model. TPT-CuCl(2) induces significant apoptosis in HeLa cell line characterized by DNA fragmentation and chromosome condensation. Comet assay revealed that TPT-CuCl(2) targets and causes severe damage to the DNA. Treatment of HeLa cells with TPT-CuCl(2) rescues the accumulation of p53 from the suppression of human papilloma virus E6, resulting in a dramatic up-regulation of Bax and Bak and down-regulation of the antiapoptotic factor Survivin. Apoptotic induction by TPT-CuCl(2) was shown to mediate in a p53-depedent manner; loss of p53 impairs the release of cytochrome c and Smac/DIABLO from mitochondria to cytosol. Moreover, we have shown that TPT-CuCl(2) induced-apoptosis was through an intrinsic mitochondrial pathway, which was inhibited by viral oncoprotein E1B19K. Caspase-3 was found to be indispensable in TPT-CuCl(2)-triggered apoptosis signaling pathway, because caspase-3 deficient cell line MCF-7 was resistant to TPT-CuCl(2). Furthermore, in vivo studies using C6 glioblastoma xenograft rat model revealed that TPT-CuCl(2) exhibits significant antiproliferative activity against tumor development with minimal cytotoxicity toward normal physiological function of the experimental rats. These findings imply the attractiveness of TPT-CuCl(2) as a drug candidate for further development.

Research paper thumbnail of Elucidating the Interaction of Enantiomeric Cu(Ii) Complexes with DNA, Rna and Hsa: A Comparative Study

Research paper thumbnail of Synthesis, Characterization, and Kinetics of Mono- and Heterobimetallic Complexes of Bis(5-nitroindazolyl) Methane Towards CTDNA

Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry

A new ligand bis(5-nitroindazolyl) methane has been synthesized and characterized by the elementa... more A new ligand bis(5-nitroindazolyl) methane has been synthesized and characterized by the elemental analysis, I.R., H, andC n.m.r. spectroscopy. A series of transition metal complexes have been prepared and new bimetallic complexes of CuII and CoII with organotin(IV) were also synthesized. All complexes have been characterized by various physico-chemical methods. The reaction kinetics of monometallic (C30H20N14O14Cu) and the bimetallic complexes

Research paper thumbnail of Recent advances in metallodrug-like molecules targeting non-coding RNAs in cancer chemotherapy

Coordination Chemistry Reviews

Research paper thumbnail of Cadmium-induced neurodegeneration and activation of noncanonical sonic hedgehog pathway in rat cerebellum

Journal of Biochemical and Molecular Toxicology

Cadmium is a nonessential toxic heavy metal, which enters the body easily and damages the cellula... more Cadmium is a nonessential toxic heavy metal, which enters the body easily and damages the cellular system. The sonic hedgehog (Shh) signaling pathway is one of the key regulatory pathways, which define neural growth and development. This study aimed to explore how cadmium exposure affects neural activities, Shh signaling cascade, and its downstream target genes. Total 18 male Wistar rats were randomly divided into two groups, control and test groups. Test rats were administered with 3 mg cadmium/kg body weight, while the control rats were treated with vehicle continuously for 28 days. Thereafter, rats were killed and the isolated brain samples were examined using oxidative stress assessment, histological and immunohistological behavioral assessment, polymerase chain reaction (PCR), and the comet assay. A disturbed oxidative balance, DNA damage, and an upregulated Shh signaling pathway were observed in cadmium-treated samples. Loss of structural integrity in cerebellum and loss of motor activity were observed in cadmium-treated rats.

Research paper thumbnail of A zwitterionic Zn(II) benzothiazole nanohybrid conjugate as hydrolytic DNA cleavage agent

Inorganic Chemistry Communications

Research paper thumbnail of {"__content__"=>"-Carboline Silver Compound Binding Studies with Human Serum Albumin: A Comprehensive Multispectroscopic Analysis and Molecular Modeling Study.", "i"=>{"__content__"=>"β"}}

Bioinorganic chemistry and applications, 2018

β-Carbolines (βCs) belong to the naturally occurring alkaloid family, derived from 9H-pyrido[3,4-... more β-Carbolines (βCs) belong to the naturally occurring alkaloid family, derived from 9H-pyrido[3,4-b]indole, also known as norharmane (Hnor). Knowing the importance of the βCs alkaloid family in biological processes, a comprehensive binding study is reported of four Ag(I) compounds containing the ligand Hnor and having different counteranions, namely, NO 3 − , ClO 4 − , BF 4 − , and PF 6 − , with human serum albumin (HSA) as a model protein. Different approaches like UV-visible, fluorescence spectroscopy, circular dichroism (CD), and molecular docking studies have been used for this purpose. e fluorescence results establish that the phenomenon of binding of Ag(Hnor) complexes to HSA can be deduced from the static quenching mechanism. e results showed a significant binding propensity of the used Ag(I) compounds towards HSA. e role of the counteranion on the binding of Ag(I) compounds to HSA appeared to be remarkable. Compounds with (ClO 4 −) and (NO 3 −) were found to have the most efficient binding towards HSA as compared to BF 4 − and PF 6 −. Circular dichroism (CD) studies made clear that conformational changes in the secondary structure of HSA were induced by the presence of Ag(I) compounds. Also, the α-helical structure of HSA was found to get transformed into a β-sheeted structure. Interestingly, (ClO 4 −) and (NO 3 −) compounds were found to induce most substantial changes in the secondary structure of HSA. e outcome of this study may contribute to understanding the propensity of proteins involved in neurological diseases (such as Alzheimer's and Parkinson's diseases) to undergo a similar transition in the presence of Ag-β-carboline compounds.

Research paper thumbnail of Loss of DUSP3 activity radiosensitizes human tumor cell lines via attenuation of DNA repair pathways

Biochimica et biophysica acta, Jul 4, 2017

Radiotherapy causes the regression of many human tumors by increasing DNA damage, and the novel m... more Radiotherapy causes the regression of many human tumors by increasing DNA damage, and the novel molecular mechanisms underlying the genomic instability leading to cancer progression and metastasis must be elucidated. Atypical dual-specificity phosphatase 3 (DUSP3) has been shown to down-regulate mitogen-activated protein kinases (MAPKs) to control the proliferation and apoptosis of human cancer cells. We have recently identified novel molecular targets of DUSP3 that function in DNA damage response and repair; however, whether DUSP3 affects these processes remains unknown. Tumor cell lines in which DUSP3 activity was suppressed by pharmacological inhibitors or a targeted siRNA were exposed to gamma radiation, and proliferation, survival, DNA strand breaks and recombination repair pathways were sequentially analyzed. The combination of reduced DUSP3 activity and gamma irradiation resulted in decreased cellular proliferation and survival and increased cellular senescence compared with ...

Research paper thumbnail of Heteroleptic Copper(I) Complexes of “Scorpionate” Bis-pyrazolyl Carboxylate Ligand with Auxiliary Phosphine as Potential Anticancer Agents: An Insight into Cytotoxic Mode

Scientific Reports, 2017

New copper(I) complexes [CuCl(PPh 3)(L)] (1: L = L A = 4-carboxyphenyl)bis(3,5-dimethylpyrazolyl)... more New copper(I) complexes [CuCl(PPh 3)(L)] (1: L = L A = 4-carboxyphenyl)bis(3,5-dimethylpyrazolyl) methane; (2: L = L B = 3-carboxyphenyl)bis(3,5-dimethylpyrazolyl)methane) were prepared and characterised by elemental analysis and various spectroscopic techniques such as FT-IR, NMR, UV-Vis, and ESI-MS. The molecular structures of complexes 1 and 2 were analyzed by theoretical B3LYP/DFT method. Furthermore, in vitro DNA binding studies were carried out to check the ability of complexes 1 and 2 to interact with native calf thymus DNA (CT-DNA) using absorption titration, fluorescence quenching and circular dichroism, which is indicative of more avid binding of the complex 1. Moreover, DNA mobility assay was also conducted to study the concentration-dependent cleavage pattern of pBR322 DNA by complex 1, and the role of ROS species to have a mechanistic insight on the cleavage pattern, which ascertained substantial roles by both hydrolytic and oxidative pathways. Additionally, we analyzed the potential of the interaction of complex 1 with DNA and enzyme (Topo I and II) with the aid of molecular modeling. Furthermore, cytotoxic activity of complex 1 was tested against HepG2 cancer cell lines. Thus, the potential of the complex 1 is promising though further in vivo investigations may be required before subjecting it to clinical trials. Cancer is ranked the second most common cause of death, only after cardiovascular diseases. Hepatocellular carcinoma or hepatic/liver cancer is the sixth most widespread cancer and the third leading cause of cancer-associated deaths 1. In the year 2016, in the USA alone, new cases and deaths due to liver/intrahepatic bile duct cancer were found to be 39230 (incidence) and 27170 (mortality) 2. Several research efforts have been made to deal with liver cancer, which include the area of metal-based drugs for cancer chemotherapy. The field of metallodrugs came to be recognized after the foundation laid by the serendipitous discovery of cisplatin (cis-diamminedichloroplatinum(II)). Cisplatin exhibited wide applications as a chemotherapeutic agent, but it has also been found to produce severe side effects 3-9. Since then there has been a hectic search for better metal-based cancer chemotherapeutic drugs. The unique properties of metal ions can be taken to advantage in

Research paper thumbnail of Synthesis of carbohydrate-conjugate heterobimetallic CuII-SnIV2 and ZnII-SnIV2 complexes; their interactions with CT DNA and nucleotides; DNA cleavage, in-vitro cytotoxicity

European Journal of Medicinal Chemistry, 2010

The new heterobimetallic Ni II eSn 2 IV (1), Cu II eSn 2 IV (2) and Zn II eSn 2 IV (3) complexes,... more The new heterobimetallic Ni II eSn 2 IV (1), Cu II eSn 2 IV (2) and Zn II eSn 2 IV (3) complexes, containing D-glucosamine, 1,8-diamino-3,6-diazaoctane and imidazole were isolated and characterized by spectral and analytical methods. The proposed geometry of Ni(II) and Cu(II) in 1 and 2 was square pyramidal, Zn (II) in 3 exhibited tetrahedral while Sn(IV) exhibits hexacoordinate environment, respectively. The X-ray powder diffraction (XRPD) confirmed the amorphous nature of all the complexes. The interaction studies of 2 and 3 with CT DNA were carried out by various biophysical techniques to show the mode of binding. The interaction of 2 and 3 with nucleotides viz 5 0-GMP and 5 0-TMP, respectively were further confirmed by 1 H, 31 P and 119 Sn NMR spectroscopy. The complex 2 exhibited effective cleavage activity with pBR322 DNA. Furthermore, the cytotoxicity of 2 was examined on a panel of human tumor cell lines of different histological origins and showed good activity against Colo205 and A2780 (GI50 < 10 mg/ml).

Research paper thumbnail of Synthesis and crystal structure elucidation of new copper(II)-based chemotherapeutic agent coupled with 1,2-DACH and orthovaniline: Validated by in vitro DNA/HSA binding profile and pBR322 cleavage pathway

Journal of photochemistry and photobiology. B, Biology, Jan 2, 2016

New copper(II)-based complex (1) was synthesized and characterized by analytical, spectroscopic a... more New copper(II)-based complex (1) was synthesized and characterized by analytical, spectroscopic and single crystal X-ray diffraction. The in vitro binding studies of complex 1 with CT DNA and HSA have been investigated by employing biophysical techniques to examine the binding propensity of 1 towards DNA and HSA. The results showed that 1 avidly binds to CT DNA via electrostatic mode along with the hydrogen bonding interaction of NH2 and CN groups of Schiff base ligand with the base pairs of DNA helix, leads to partial unwinding and destabilization of the DNA double helix. Moreover, the CD spectral studies revealed that complex 1 binds through groove binding interaction that stabilizes the right-handed B-form of DNA. Complex 1 showed an impressive photoinduced nuclease activity generating single-strand breaks in comparison with the DNA cleavage activity in presence of visible light. The mechanistic investigation revealed the efficiency of 1 to cleave DNA strands by involving the gen...

Research paper thumbnail of A Chloro-Bridged Heterobimetallic (η6-Arene)ruthenium–Organotin Complex as an Efficient Topoisomerase Iα Inhibitor

Organometallics, Apr 18, 2013

ABSTRACT The chloro-bridged heterobimetallic complex (η6-hexamethylbenzene)Ru(dmp)(μ-Cl)2Sn(CH3)2... more ABSTRACT The chloro-bridged heterobimetallic complex (η6-hexamethylbenzene)Ru(dmp)(μ-Cl)2Sn(CH3)2Cl2 was designed, synthesized, and characterized by various spectroscopic methods, viz. IR, 1H and 13C NMR, and ESI MS, and single-crystal X-ray crystallography as an approach toward multitargeting metal-based potential anticancer drug candidates. In vitro DNA binding studies confirmed the binding affinity of the complex toward the minor groove of DNA, which is further validated by docking studies. Furthermore, the complex exhibited significant inhibitory effects on topoisomerase Iα at a very low concentration (8 μM). The cytotoxicity of the complex against HeLa and HepG2 cancer cell lines was evaluated, which revealed significant regression in cancerous cells in comparison with the standard drug.

Research paper thumbnail of Synthesis, characterization, solution stability studies, electrochemistry, and DNA-binding behavior of Cu(II) complexes of D-gluconic acid

Journal of Carbohydrate Chemistry, Nov 1, 2005

Research paper thumbnail of Synthesis and characterization of Co( ii ) and Fe( ii ) peptide conjugates as hydrolytic cleaving agents and their preferential enantiomeric disposition for CT-DNA: structural investigation of l -enantiomers by DFT and molecular docking studies

RSC Adv., 2015

Molecular docked model of Co(ii) peptide conjugate with DNA and the mechanism of hydrolytic cleav... more Molecular docked model of Co(ii) peptide conjugate with DNA and the mechanism of hydrolytic cleavage of pBR322 DNA.

Research paper thumbnail of Investigation of diorganotin(IV) complexes: Synthesis, characterization, in vitro DNA binding studies and cytotoxicity assessment of di-n-butyltin(IV) complex

Inorganica Chimica Acta, 2014

Research paper thumbnail of Synthesis and spectroscopic characterization of diorganotin( iv ) complexes of N′-(4-hydroxypent-3-en-2-ylidene)isonicotinohydrazide: chemotherapeutic potential validation by in vitro interaction studies with DNA/HSA, DFT, molecular docking and cytotoxic activity

RSC Adv., 2015

A diorganotin(iv) hydrazide complex as a potential cancer chemotherapeutic agent targeting DNA us... more A diorganotin(iv) hydrazide complex as a potential cancer chemotherapeutic agent targeting DNA using the carrier protein HSA.