Humaira Nadeem | Riphah International University (original) (raw)

Papers by Humaira Nadeem

Research paper thumbnail of Enantioselective Synthesis, Computational Molecular Docking and Invitro Anticoagulant Activity of Warfarin-Based Derivatives

Warfarin containing coumarin ring system possesses excellent anticoagulant activity in its enanti... more Warfarin containing coumarin ring system possesses excellent anticoagulant activity in its enantiomeric form (S). The present work designed to synthesize warfarin based derivatives enantioselectivily to explore their anticoagulant potential. The substituted chalcones were reacted with 4-OH coumarin in presence of chiral catalyst 9-amino-9-deoxyepiquinine to afford warfarin based analogues 5a-5k. The structures of synthesized compounds 5a-5k were confirmed by FTIR, 1HNMR,13CNMR and EIMS data. The enantioselectivity has been assured by determining the enantiomeric excess (ee) in chiral HPLC which exhibited 16-99%ee. The invitro anticoagulant activity of synthesized compounds 5a-5k was evaluated by plasma recalcification time (PRT) method and it was found that most of the derivatives showed good anticoagulant activity specifically compound 5b exhibited excellent results compared to warfarin. The compound 5b displayed IC50 value 249.88µM better than standard warfarin (IC50 408.70µM). Th...

Research paper thumbnail of Enantioselective Synthesis, Tautomerism, Molecular Docking And Biological Evaluation of 4-Hydroxy-3-(3-Oxo-1-Phenylbutyl)-2H-Chromen-2-One Analogues

Keeping in view the aim of better alternatives of 4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-chromen-2-... more Keeping in view the aim of better alternatives of 4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-chromen-2-one (warfarin), eleven analogs of warfarin have been synthesized with the goal to increase enantioselectivity of (S) enantiomer by using appropriate catalyst and minimize tautomerism by replacing methyl group of the side chain with aryl group. There are many reports of the serious complications with warfarin use, which are associated with the tautomeric forms of warfarin. The key step was highly enantioselective Michael addition of variously substituted chalcone and 4-hydroxycoumarin by using cinchona based 9-amino-9-deoxyepiquinine as chiral catalyst. Synthesized compounds were characterized by IR, 1HNMR,13CNMR, EIMS and CD studies. Enantiomeric excess (%ee) was determined by chiral HPLC which was upto 98%. Synthesized analogues were screened for anticoagulant, antibacterial and antifungal activities. In-vitro anticoagulant activity was evaluated by plasma recalcification time (PRT) met...

Research paper thumbnail of Thiazolidine Derivatives Attenuate Carrageenan-Induced Inflammatory Pain in Mice

Drug Design, Development and Therapy, 2021

Background Peripheral inflammation leads to the development of persistent thermal hyperalgesia an... more Background Peripheral inflammation leads to the development of persistent thermal hyperalgesia and mechanical allodynia associated with increased expression of interleukin-1β (IL-1β) in the spinal cord. The aim of the present study was to investigate the effects of thiazolidine derivatives, 1b ([2-(2-hydroxyphenyl)-1,3-thiazolidin-4-yl](morpholin-4-yl)methanone) and 1d (2-hydroxy-4-{[2-(2-hydroxyphenyl)-1,3-thiazolidine-4-carbonyl]amino}benzoic acid), on thermal hyperalgesia, mechanical allodynia and on IL-1β expression during carrageenan-induced inflammation in the spinal cord in mice. Inflammatory pain was induced by injecting 1% carrageenan into the right hind paw of the mice. Methods The animals were administered thiazolidine derivatives, 1b and 1d (1 mg/kg, 3 mg/kg, or 10 mg/kg), intraperitoneally 30 minutes before carrageenan administration. The animals’ behavior was evaluated by measuring thermal hyperalgesia, mechanical allodynia, and motor coordination. The IL-1β expression...

Research paper thumbnail of Computational drug designing of newly synthesized triazoles against potential targets of methicillin resistant Staphylococcus aureus

Methicillin resistant Staphylococcus aureus (MRSA) is resistant to known antibiotics and has beco... more Methicillin resistant Staphylococcus aureus (MRSA) is resistant to known antibiotics and has become a great challenge for healthcare professionals, therefore new molecules are needed to manage this situation. In this study, new lead molecules 4-Amino-5-(2-Hydroxyphenyl)-1,2,4-Triazol-3-Thione (U1) and4-(2-hydroxybenzalidine) amine-5-(2hydroxy) phenyl-1,2,4-triazole-3-thiol(U1A Schiff base) were synthesized by fusion method that showed promising antibacterial activity (U1A: 26mm and U1: 14mm) against MRSA.FT-IR and NMR were used for structural characterization of these derivatives and their toxicity properties were assessed by Lipinski’s rule of 5. New potential drug targets of this bacterium were also identified by comparative and subtraction genomics techniques. In particular, octanoyl-[GcvH]: protein N-octanoyl transferase and phosphor mevalonate kinase were used as potential targets in AutoDock Vina studies. This study can provide a framework to find potential drug targets for ot...

Research paper thumbnail of Synthesis, Molecular Docking and Pharmacological Investigation of Heterocyclic Amine Derivatives as Potential Anticancer Agents

Cancer is life threatening disease that causes great damage to health worldwide. Studies shown th... more Cancer is life threatening disease that causes great damage to health worldwide. Studies shown that hypoxia is the major contributor to tumor and cancer development due to overexpression of carbonic anhydrase. To encounter such cells abnormalities, demanding new drugs or novel analogs of currently in use. Therefore, the search for new pharmacoactive moieties with considerable effective activity against such tumors and cancers is needed. The implication of heterocyclic amine and acetamide derivatives well known as chemotherapeutic agents. Heterocyclic amine morpholine was taken as principal products and its new derivatives were synthesized after being designed computationally via molecular docking. A series of some of its new synthetic analogs i.e heterocyclic amine derivatives 1(a-o) were successfully synthesized and screened for their anticancer and carbonic anhydrase inhibitory potential. Most of the compounds showed good results possessing reasonable carbonic anhydrase inhibitory...

Research paper thumbnail of Screening of Synthetic Isoxazolone Derivative Role in Alzheimer’s Disease: Computational and Pharmacological Approach

Research paper thumbnail of Synthesis and Biological Evaluation of Benzimidazole Derivatives as Potential Neuroprotective Agents in an Ethanol-Induced Rodent Model

ACS Chemical Neuroscience

Research paper thumbnail of Isatin-hydrazide conjugates as potent α-amylase and α-glucosidase inhibitors: Synthesis, structure and in vitro evaluations

Research paper thumbnail of Anti-hyperglycemic activity of Heliotropium strigosum (Boraginaecae) whole plant extract in alloxan-induced diabetic mice

Tropical Journal of Pharmaceutical Research

Purpose: To investigate Heliotropium strigosum whole plant extract for its potential to reduce th... more Purpose: To investigate Heliotropium strigosum whole plant extract for its potential to reduce the blood glucose level of alloxan-induced diabetic mice.Methods: Preliminary phytochemical analysis was carried out using standard procedures. Diabetes was induced in Balb/c mice by injecting alloxan (200 mg/kg i.p.). The crude methanol extract of Heliotropium strigosum (Hs.Cr, 30, 100 and 300 mg/kg doses) was administered daily to alloxan-induced diabetic mice for 15 days and its effect on fasting blood glucose levels, body weight and oral glucose tolerancewas evaluated. Two control groups (non-diabetic control and diabetic control) received normal saline (0.2 ml). Metformin (500 mg/kg) was used as reference standard.Results: Heliotropium strigosum showed positive for the presence of alkaloids, tannins and flavonoids. The extract (30, 100 and 300 mg/kg) caused significant reduction in the fasting blood glucose level of alloxan-induced diabetic mice on days 5, 10 and 15 compared to diab...

Research paper thumbnail of Genome wide meta-analysis of cDNA datasets reveals new target gene signatures of colorectal cancer based on systems biology approach

Journal of Biological Research-Thessaloniki

Background Colorectal cancer is known to be the most common type of cancer worldwide with high di... more Background Colorectal cancer is known to be the most common type of cancer worldwide with high disease-related mortality. It is the third most common cancer in men and women and is the second major cause of death globally due to cancer. It is a complicated and fatal disease comprising of a group of molecular heterogeneous disorders. Results This study identifies the potential biomarkers of CRC through differentially expressed analysis, system biology, and proteomic analysis. Ten publicly available microarray datasets were analyzed and seven potential biomarkers were identified from the list of differentially expressed genes having a p value

Research paper thumbnail of Schiff-Based Metal Complexes of Lamotrigine: Design Synthesis, Characterization, and Biological Evaluation

In the current study, a series of Schiff base derivatives of lamotrigine are complexed with zinc,... more In the current study, a series of Schiff base derivatives of lamotrigine are complexed with zinc, copper, silver, and tin and characterized by spectroscopic techniques and biological assays. Docking analyses revealed six complexes with favorable binding interactions, which were further subjected to in vitro anticancer activity. The complexes 6b and 6c displayed the most potent antiproliferative activity against MCF-7 cell lines with an IC 50 value of 11.9 ± 0.27 and 12.0 ± 0.14 μM, respectively, as compared with the standard doxorubicin with an IC 50 value of 0.90 ± 0.14 μM. In vivo anticonvulsant activities of the compounds were evaluated by the subcutaneous pentylenetetrazole model and neurotoxic activities by the minimal motor impairment model. The neurotoxicity of targeted compounds was measured using the rotating rod (ROT) method. Computational studies were carried out using the reported crystal structures of multidrug-resistant protein (PDB-ID: 2KAV) and dihydrofolate reductase (PDB-ID: 3GHW), indicating that the compound 6c showed significant interactions at the voltage-gated sodium ion channel in the brain and at dihydrofolate reductase enzyme in the breast. Certain metal complexes of Schiff base ligands (e.g., 6c) were found to possess the most potent anticancer, anticonvulsant, and neurotoxic potential than lamotrigine alone.

Research paper thumbnail of Genome-scale meta-analysis of breast cancer datasets identifies promising targets for drug development

Journal of Biological Research-Thessaloniki

Background Because of the highly heterogeneous nature of breast cancer, each subtype differs in r... more Background Because of the highly heterogeneous nature of breast cancer, each subtype differs in response to several treatment regimens. This has limited the therapeutic options for metastatic breast cancer disease requiring exploration of diverse therapeutic models to target tumor specific biomarkers. Methods Differentially expressed breast cancer genes identified through extensive data mapping were studied for their interaction with other target proteins involved in breast cancer progression. The molecular mechanisms by which these signature genes are involved in breast cancer metastasis were also studied through pathway analysis. The potential drug targets for these genes were also identified. Results From 50 DEGs, 20 genes were identified based on fold change and p-value and the data curation of these genes helped in shortlisting 8 potential gene signatures that can be used as potential candidates for breast cancer. Their network and pathway analysis clarified the role of these g...

Research paper thumbnail of Synergistic Cytotoxic Effect from Combination of Wedelolactone and Cisplatin in HeLa Cell Line: A Novel Finding

Drug Design, Development and Therapy

Context and Objective: Cisplatin is a platinum drug in current clinical use for the treatment of ... more Context and Objective: Cisplatin is a platinum drug in current clinical use for the treatment of cervical cancer. However, drug toxicity and resistance are its two major limitations. The aim of this investigation was to test the cytotoxic activity of potential phytochemicals alone and in combination with cisplatin in cervical cancer cells. Methods: In this study, cytotoxicity of phytochemicals including wedelolactone (WDL), betulinic acid (BA) and epigallocatechin gallate (EGCG) was investigated in human cervical cancer cell line HeLa through 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) reduction assay. Combined drug action resulting from the combination of cisplatin with WDL and BA was investigated in the same cell line through median effect principle. The combination index (CI) was taken as a measure of combined drug action. Results: BA resulted in synergistic outcome when co-administered with cisplatin at 0/0 time; (bolus administration) while administration of either drug (cisplatin or BA) four hours before the other (0/4 or 4/0) resulted in antagonistic action. WDL, on the other hand, was found out to be synergistic at any of the applied sequence of drug administration (0/0, 0/4 or 4/0). Discussion and Conclusion: This is the first study reporting cytotoxic activity of WDL in HeLa cells either as single agent or in combination with cisplatin. These results support the idea that sequential combination of cisplatin with WDL and BA may work effectively in cervical cancer cells.

Research paper thumbnail of Rhodanine-3-Acetamide Derivatives as Aldose and Aldehyde Reductase Inhibitors to Treat Diabetic Complications; Synthesis, Biological Evaluation and Molecular Docking Studies

In diabetes, increased accumulation of sorbitol has been associated with diabetic complications t... more In diabetes, increased accumulation of sorbitol has been associated with diabetic complications through polyol pathway. Aldose reductase (AR) is one of the key factors involved in reduction of glucose to sorbitol, thereby its inhibition is considered to be important for the management of diabetic complications. In the present study, a series of seven 4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetamide derivatives 3(a-g) were synthesized by the reaction of 5-(4-hydroxy-3-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2a) and 5-(4-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2b) with different amines. The synthesized compounds 3(a-g) were investigated for their in vitro aldehyde reductase (ALR1) and aldose reductase (ALR2) enzyme inhibitory potential. Compound 3c, 3d, 3e, and 3f showed ALR1 inhibition at lower micromolar concentration whereas all the compounds were more active than the standard inhibitor valproic acid. Most of the compounds were...

Research paper thumbnail of Formulation of ferrous fumarate (combination) tablets by using a direct-compression method

Indian Journal of Science and Technology

Ferrous fumarate has poor flow properties which cause compression problems. When ferrous fumarate... more Ferrous fumarate has poor flow properties which cause compression problems. When ferrous fumarate is manufactured in combination with folic acid, the same problem is encountered. Therefore, a wet-granulation method is used for tablet manufacturing, which is a time-consuming and energy-wasting process compared to a directcompression method. In the present work, ferrous fumarate and folic acid (combination) tablets have been prepared using an optimized direct-compression technique that decreases the total manufacturing time of a batch (approx. 1.5 million tablets) from 24-28 h to only 2-3 h. The direct-compression technique is a simple and cost-effective method of manufacturing ferrous fumarate and folic acid (combination) tablets. Several formulations were developed using different proportions of avicel PH102, talcum, magnesium stearate, sodium lauryl sulfate, sugar, primojel, lactose, PVPK-30 and aerosil. Ten formulations were found to fulfill the specified criteria.

Research paper thumbnail of Benzimidazole Derivative Ameliorates Opioid-mediated Tolerance during Anticancer-Induced Neuropathic Pain in mice

Anti-Cancer Agents in Medicinal Chemistry

Background: Cancer is known to be the second significant cause of death worldwide. Chemotherapeut... more Background: Cancer is known to be the second significant cause of death worldwide. Chemotherapeutic agents such as platinum-based compounds are frequently used single-handedly or accompanied with additional chemotherapies to treat cancer patients. Chemotherapy-inducedperipheral painful neuropathy is seen in around 40% of patient who are treated with platinum-based compounds including cisplatin. This not only decreases quality of life of patients but also patients’ compliance to cisplatin. Objectives: Nalbuphine, an opioid, is frequently used to treat acute and chronic pain coupled with cisplatin in cancer patients. However, long term use of nalbuphine induces tolerance to its analgesic effects. We employed the same strategy to induce tolerance in mice. Methods: Here, we investigated analgesic effects of 2-[(pyrrolidin-1-yl) methyl]-1H-benzimidazole (BNZ), a benzimidazole derivative, on nalbuphine-induced tolerance during cisplatin-induced neuropathic pain using hot plate test, tail ...

Research paper thumbnail of Amino acid conjugates of 2-mercaptobenzimidazole provide better anti-inflammatory pharmacology and improved toxicity profile

Drug Development Research

Research paper thumbnail of Investigation of antioxidant and anti‐nociceptive potential of isoxazolone, pyrazolone derivatives, and their molecular docking studies

Drug Development Research

Research paper thumbnail of Correction to: Genome wide meta-analysis of cDNA datasets reveals new target gene signatures of colorectal cancer based on systems biology approach

Journal of Biological Research-Thessaloniki

Research paper thumbnail of Post-Treatment of Synthetic Polyphenolic 1,3,4 Oxadiazole Compound A3, Attenuated Ischemic Stroke-Induced Neuroinflammation and Neurodegeneration

Biomolecules

Ischemic stroke is categorized by either permanent or transient blood flow obstruction, impeding ... more Ischemic stroke is categorized by either permanent or transient blood flow obstruction, impeding the distribution of oxygen and essential nutrients to the brain. In this study, we examined the neuroprotective effects of compound A3, a synthetic polyphenolic drug product, against ischemic brain injury by employing an animal model of permanent middle cerebral artery occlusion (p-MCAO). Ischemic stroke induced significant elevation in the levels of reactive oxygen species and, ultimately, provoked inflammatory cascade. Here, we demonstrated that A3 upregulated the endogenous antioxidant enzymes, such as glutathione s-transferase (GST), glutathione (GSH), and reversed the ischemic-stroke-induced nitric oxide (NO) and lipid peroxidation (LPO) elevation in the peri-infarct cortical and striatal tissue, through the activation of endogenous antioxidant nuclear factor E2-related factor or nuclear factor erythroid 2 (Nrf2). In addition, A3 attenuated neuroinflammatory markers such as ionized ...

Research paper thumbnail of Enantioselective Synthesis, Computational Molecular Docking and Invitro Anticoagulant Activity of Warfarin-Based Derivatives

Warfarin containing coumarin ring system possesses excellent anticoagulant activity in its enanti... more Warfarin containing coumarin ring system possesses excellent anticoagulant activity in its enantiomeric form (S). The present work designed to synthesize warfarin based derivatives enantioselectivily to explore their anticoagulant potential. The substituted chalcones were reacted with 4-OH coumarin in presence of chiral catalyst 9-amino-9-deoxyepiquinine to afford warfarin based analogues 5a-5k. The structures of synthesized compounds 5a-5k were confirmed by FTIR, 1HNMR,13CNMR and EIMS data. The enantioselectivity has been assured by determining the enantiomeric excess (ee) in chiral HPLC which exhibited 16-99%ee. The invitro anticoagulant activity of synthesized compounds 5a-5k was evaluated by plasma recalcification time (PRT) method and it was found that most of the derivatives showed good anticoagulant activity specifically compound 5b exhibited excellent results compared to warfarin. The compound 5b displayed IC50 value 249.88µM better than standard warfarin (IC50 408.70µM). Th...

Research paper thumbnail of Enantioselective Synthesis, Tautomerism, Molecular Docking And Biological Evaluation of 4-Hydroxy-3-(3-Oxo-1-Phenylbutyl)-2H-Chromen-2-One Analogues

Keeping in view the aim of better alternatives of 4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-chromen-2-... more Keeping in view the aim of better alternatives of 4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-chromen-2-one (warfarin), eleven analogs of warfarin have been synthesized with the goal to increase enantioselectivity of (S) enantiomer by using appropriate catalyst and minimize tautomerism by replacing methyl group of the side chain with aryl group. There are many reports of the serious complications with warfarin use, which are associated with the tautomeric forms of warfarin. The key step was highly enantioselective Michael addition of variously substituted chalcone and 4-hydroxycoumarin by using cinchona based 9-amino-9-deoxyepiquinine as chiral catalyst. Synthesized compounds were characterized by IR, 1HNMR,13CNMR, EIMS and CD studies. Enantiomeric excess (%ee) was determined by chiral HPLC which was upto 98%. Synthesized analogues were screened for anticoagulant, antibacterial and antifungal activities. In-vitro anticoagulant activity was evaluated by plasma recalcification time (PRT) met...

Research paper thumbnail of Thiazolidine Derivatives Attenuate Carrageenan-Induced Inflammatory Pain in Mice

Drug Design, Development and Therapy, 2021

Background Peripheral inflammation leads to the development of persistent thermal hyperalgesia an... more Background Peripheral inflammation leads to the development of persistent thermal hyperalgesia and mechanical allodynia associated with increased expression of interleukin-1β (IL-1β) in the spinal cord. The aim of the present study was to investigate the effects of thiazolidine derivatives, 1b ([2-(2-hydroxyphenyl)-1,3-thiazolidin-4-yl](morpholin-4-yl)methanone) and 1d (2-hydroxy-4-{[2-(2-hydroxyphenyl)-1,3-thiazolidine-4-carbonyl]amino}benzoic acid), on thermal hyperalgesia, mechanical allodynia and on IL-1β expression during carrageenan-induced inflammation in the spinal cord in mice. Inflammatory pain was induced by injecting 1% carrageenan into the right hind paw of the mice. Methods The animals were administered thiazolidine derivatives, 1b and 1d (1 mg/kg, 3 mg/kg, or 10 mg/kg), intraperitoneally 30 minutes before carrageenan administration. The animals’ behavior was evaluated by measuring thermal hyperalgesia, mechanical allodynia, and motor coordination. The IL-1β expression...

Research paper thumbnail of Computational drug designing of newly synthesized triazoles against potential targets of methicillin resistant Staphylococcus aureus

Methicillin resistant Staphylococcus aureus (MRSA) is resistant to known antibiotics and has beco... more Methicillin resistant Staphylococcus aureus (MRSA) is resistant to known antibiotics and has become a great challenge for healthcare professionals, therefore new molecules are needed to manage this situation. In this study, new lead molecules 4-Amino-5-(2-Hydroxyphenyl)-1,2,4-Triazol-3-Thione (U1) and4-(2-hydroxybenzalidine) amine-5-(2hydroxy) phenyl-1,2,4-triazole-3-thiol(U1A Schiff base) were synthesized by fusion method that showed promising antibacterial activity (U1A: 26mm and U1: 14mm) against MRSA.FT-IR and NMR were used for structural characterization of these derivatives and their toxicity properties were assessed by Lipinski’s rule of 5. New potential drug targets of this bacterium were also identified by comparative and subtraction genomics techniques. In particular, octanoyl-[GcvH]: protein N-octanoyl transferase and phosphor mevalonate kinase were used as potential targets in AutoDock Vina studies. This study can provide a framework to find potential drug targets for ot...

Research paper thumbnail of Synthesis, Molecular Docking and Pharmacological Investigation of Heterocyclic Amine Derivatives as Potential Anticancer Agents

Cancer is life threatening disease that causes great damage to health worldwide. Studies shown th... more Cancer is life threatening disease that causes great damage to health worldwide. Studies shown that hypoxia is the major contributor to tumor and cancer development due to overexpression of carbonic anhydrase. To encounter such cells abnormalities, demanding new drugs or novel analogs of currently in use. Therefore, the search for new pharmacoactive moieties with considerable effective activity against such tumors and cancers is needed. The implication of heterocyclic amine and acetamide derivatives well known as chemotherapeutic agents. Heterocyclic amine morpholine was taken as principal products and its new derivatives were synthesized after being designed computationally via molecular docking. A series of some of its new synthetic analogs i.e heterocyclic amine derivatives 1(a-o) were successfully synthesized and screened for their anticancer and carbonic anhydrase inhibitory potential. Most of the compounds showed good results possessing reasonable carbonic anhydrase inhibitory...

Research paper thumbnail of Screening of Synthetic Isoxazolone Derivative Role in Alzheimer’s Disease: Computational and Pharmacological Approach

Research paper thumbnail of Synthesis and Biological Evaluation of Benzimidazole Derivatives as Potential Neuroprotective Agents in an Ethanol-Induced Rodent Model

ACS Chemical Neuroscience

Research paper thumbnail of Isatin-hydrazide conjugates as potent α-amylase and α-glucosidase inhibitors: Synthesis, structure and in vitro evaluations

Research paper thumbnail of Anti-hyperglycemic activity of Heliotropium strigosum (Boraginaecae) whole plant extract in alloxan-induced diabetic mice

Tropical Journal of Pharmaceutical Research

Purpose: To investigate Heliotropium strigosum whole plant extract for its potential to reduce th... more Purpose: To investigate Heliotropium strigosum whole plant extract for its potential to reduce the blood glucose level of alloxan-induced diabetic mice.Methods: Preliminary phytochemical analysis was carried out using standard procedures. Diabetes was induced in Balb/c mice by injecting alloxan (200 mg/kg i.p.). The crude methanol extract of Heliotropium strigosum (Hs.Cr, 30, 100 and 300 mg/kg doses) was administered daily to alloxan-induced diabetic mice for 15 days and its effect on fasting blood glucose levels, body weight and oral glucose tolerancewas evaluated. Two control groups (non-diabetic control and diabetic control) received normal saline (0.2 ml). Metformin (500 mg/kg) was used as reference standard.Results: Heliotropium strigosum showed positive for the presence of alkaloids, tannins and flavonoids. The extract (30, 100 and 300 mg/kg) caused significant reduction in the fasting blood glucose level of alloxan-induced diabetic mice on days 5, 10 and 15 compared to diab...

Research paper thumbnail of Genome wide meta-analysis of cDNA datasets reveals new target gene signatures of colorectal cancer based on systems biology approach

Journal of Biological Research-Thessaloniki

Background Colorectal cancer is known to be the most common type of cancer worldwide with high di... more Background Colorectal cancer is known to be the most common type of cancer worldwide with high disease-related mortality. It is the third most common cancer in men and women and is the second major cause of death globally due to cancer. It is a complicated and fatal disease comprising of a group of molecular heterogeneous disorders. Results This study identifies the potential biomarkers of CRC through differentially expressed analysis, system biology, and proteomic analysis. Ten publicly available microarray datasets were analyzed and seven potential biomarkers were identified from the list of differentially expressed genes having a p value

Research paper thumbnail of Schiff-Based Metal Complexes of Lamotrigine: Design Synthesis, Characterization, and Biological Evaluation

In the current study, a series of Schiff base derivatives of lamotrigine are complexed with zinc,... more In the current study, a series of Schiff base derivatives of lamotrigine are complexed with zinc, copper, silver, and tin and characterized by spectroscopic techniques and biological assays. Docking analyses revealed six complexes with favorable binding interactions, which were further subjected to in vitro anticancer activity. The complexes 6b and 6c displayed the most potent antiproliferative activity against MCF-7 cell lines with an IC 50 value of 11.9 ± 0.27 and 12.0 ± 0.14 μM, respectively, as compared with the standard doxorubicin with an IC 50 value of 0.90 ± 0.14 μM. In vivo anticonvulsant activities of the compounds were evaluated by the subcutaneous pentylenetetrazole model and neurotoxic activities by the minimal motor impairment model. The neurotoxicity of targeted compounds was measured using the rotating rod (ROT) method. Computational studies were carried out using the reported crystal structures of multidrug-resistant protein (PDB-ID: 2KAV) and dihydrofolate reductase (PDB-ID: 3GHW), indicating that the compound 6c showed significant interactions at the voltage-gated sodium ion channel in the brain and at dihydrofolate reductase enzyme in the breast. Certain metal complexes of Schiff base ligands (e.g., 6c) were found to possess the most potent anticancer, anticonvulsant, and neurotoxic potential than lamotrigine alone.

Research paper thumbnail of Genome-scale meta-analysis of breast cancer datasets identifies promising targets for drug development

Journal of Biological Research-Thessaloniki

Background Because of the highly heterogeneous nature of breast cancer, each subtype differs in r... more Background Because of the highly heterogeneous nature of breast cancer, each subtype differs in response to several treatment regimens. This has limited the therapeutic options for metastatic breast cancer disease requiring exploration of diverse therapeutic models to target tumor specific biomarkers. Methods Differentially expressed breast cancer genes identified through extensive data mapping were studied for their interaction with other target proteins involved in breast cancer progression. The molecular mechanisms by which these signature genes are involved in breast cancer metastasis were also studied through pathway analysis. The potential drug targets for these genes were also identified. Results From 50 DEGs, 20 genes were identified based on fold change and p-value and the data curation of these genes helped in shortlisting 8 potential gene signatures that can be used as potential candidates for breast cancer. Their network and pathway analysis clarified the role of these g...

Research paper thumbnail of Synergistic Cytotoxic Effect from Combination of Wedelolactone and Cisplatin in HeLa Cell Line: A Novel Finding

Drug Design, Development and Therapy

Context and Objective: Cisplatin is a platinum drug in current clinical use for the treatment of ... more Context and Objective: Cisplatin is a platinum drug in current clinical use for the treatment of cervical cancer. However, drug toxicity and resistance are its two major limitations. The aim of this investigation was to test the cytotoxic activity of potential phytochemicals alone and in combination with cisplatin in cervical cancer cells. Methods: In this study, cytotoxicity of phytochemicals including wedelolactone (WDL), betulinic acid (BA) and epigallocatechin gallate (EGCG) was investigated in human cervical cancer cell line HeLa through 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) reduction assay. Combined drug action resulting from the combination of cisplatin with WDL and BA was investigated in the same cell line through median effect principle. The combination index (CI) was taken as a measure of combined drug action. Results: BA resulted in synergistic outcome when co-administered with cisplatin at 0/0 time; (bolus administration) while administration of either drug (cisplatin or BA) four hours before the other (0/4 or 4/0) resulted in antagonistic action. WDL, on the other hand, was found out to be synergistic at any of the applied sequence of drug administration (0/0, 0/4 or 4/0). Discussion and Conclusion: This is the first study reporting cytotoxic activity of WDL in HeLa cells either as single agent or in combination with cisplatin. These results support the idea that sequential combination of cisplatin with WDL and BA may work effectively in cervical cancer cells.

Research paper thumbnail of Rhodanine-3-Acetamide Derivatives as Aldose and Aldehyde Reductase Inhibitors to Treat Diabetic Complications; Synthesis, Biological Evaluation and Molecular Docking Studies

In diabetes, increased accumulation of sorbitol has been associated with diabetic complications t... more In diabetes, increased accumulation of sorbitol has been associated with diabetic complications through polyol pathway. Aldose reductase (AR) is one of the key factors involved in reduction of glucose to sorbitol, thereby its inhibition is considered to be important for the management of diabetic complications. In the present study, a series of seven 4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetamide derivatives 3(a-g) were synthesized by the reaction of 5-(4-hydroxy-3-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2a) and 5-(4-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2b) with different amines. The synthesized compounds 3(a-g) were investigated for their in vitro aldehyde reductase (ALR1) and aldose reductase (ALR2) enzyme inhibitory potential. Compound 3c, 3d, 3e, and 3f showed ALR1 inhibition at lower micromolar concentration whereas all the compounds were more active than the standard inhibitor valproic acid. Most of the compounds were...

Research paper thumbnail of Formulation of ferrous fumarate (combination) tablets by using a direct-compression method

Indian Journal of Science and Technology

Ferrous fumarate has poor flow properties which cause compression problems. When ferrous fumarate... more Ferrous fumarate has poor flow properties which cause compression problems. When ferrous fumarate is manufactured in combination with folic acid, the same problem is encountered. Therefore, a wet-granulation method is used for tablet manufacturing, which is a time-consuming and energy-wasting process compared to a directcompression method. In the present work, ferrous fumarate and folic acid (combination) tablets have been prepared using an optimized direct-compression technique that decreases the total manufacturing time of a batch (approx. 1.5 million tablets) from 24-28 h to only 2-3 h. The direct-compression technique is a simple and cost-effective method of manufacturing ferrous fumarate and folic acid (combination) tablets. Several formulations were developed using different proportions of avicel PH102, talcum, magnesium stearate, sodium lauryl sulfate, sugar, primojel, lactose, PVPK-30 and aerosil. Ten formulations were found to fulfill the specified criteria.

Research paper thumbnail of Benzimidazole Derivative Ameliorates Opioid-mediated Tolerance during Anticancer-Induced Neuropathic Pain in mice

Anti-Cancer Agents in Medicinal Chemistry

Background: Cancer is known to be the second significant cause of death worldwide. Chemotherapeut... more Background: Cancer is known to be the second significant cause of death worldwide. Chemotherapeutic agents such as platinum-based compounds are frequently used single-handedly or accompanied with additional chemotherapies to treat cancer patients. Chemotherapy-inducedperipheral painful neuropathy is seen in around 40% of patient who are treated with platinum-based compounds including cisplatin. This not only decreases quality of life of patients but also patients’ compliance to cisplatin. Objectives: Nalbuphine, an opioid, is frequently used to treat acute and chronic pain coupled with cisplatin in cancer patients. However, long term use of nalbuphine induces tolerance to its analgesic effects. We employed the same strategy to induce tolerance in mice. Methods: Here, we investigated analgesic effects of 2-[(pyrrolidin-1-yl) methyl]-1H-benzimidazole (BNZ), a benzimidazole derivative, on nalbuphine-induced tolerance during cisplatin-induced neuropathic pain using hot plate test, tail ...

Research paper thumbnail of Amino acid conjugates of 2-mercaptobenzimidazole provide better anti-inflammatory pharmacology and improved toxicity profile

Drug Development Research

Research paper thumbnail of Investigation of antioxidant and anti‐nociceptive potential of isoxazolone, pyrazolone derivatives, and their molecular docking studies

Drug Development Research

Research paper thumbnail of Correction to: Genome wide meta-analysis of cDNA datasets reveals new target gene signatures of colorectal cancer based on systems biology approach

Journal of Biological Research-Thessaloniki

Research paper thumbnail of Post-Treatment of Synthetic Polyphenolic 1,3,4 Oxadiazole Compound A3, Attenuated Ischemic Stroke-Induced Neuroinflammation and Neurodegeneration

Biomolecules

Ischemic stroke is categorized by either permanent or transient blood flow obstruction, impeding ... more Ischemic stroke is categorized by either permanent or transient blood flow obstruction, impeding the distribution of oxygen and essential nutrients to the brain. In this study, we examined the neuroprotective effects of compound A3, a synthetic polyphenolic drug product, against ischemic brain injury by employing an animal model of permanent middle cerebral artery occlusion (p-MCAO). Ischemic stroke induced significant elevation in the levels of reactive oxygen species and, ultimately, provoked inflammatory cascade. Here, we demonstrated that A3 upregulated the endogenous antioxidant enzymes, such as glutathione s-transferase (GST), glutathione (GSH), and reversed the ischemic-stroke-induced nitric oxide (NO) and lipid peroxidation (LPO) elevation in the peri-infarct cortical and striatal tissue, through the activation of endogenous antioxidant nuclear factor E2-related factor or nuclear factor erythroid 2 (Nrf2). In addition, A3 attenuated neuroinflammatory markers such as ionized ...