Dalip Kumar - Academia.edu (original) (raw)
Papers by Dalip Kumar
Organic letters, Jan 5, 2017
Gold(III)-catalyzed synthesis of 14-π electron heteroaromatic thiopyrano[2,3-b]indole is reported... more Gold(III)-catalyzed synthesis of 14-π electron heteroaromatic thiopyrano[2,3-b]indole is reported using conjugated enyne tethered indole sulfides, featuring skeletal rearrangement conjoined with intramolecular hydroarylation (via C3-H functionalization of the indole core) and oxidative aromatization. Subsequent Pd-catalyzed C-C coupling resulted in a 16-π electron heteroaromatic isothiochromeno[1,8,7-bcd]indole.
Anti-cancer agents in medicinal chemistry, Jan 21, 2016
A new series of novel 2-arylamino-4-(3¢-indolyl)thiazoles have been designed as potent cytotoxic ... more A new series of novel 2-arylamino-4-(3¢-indolyl)thiazoles have been designed as potent cytotoxic agents. One-pot microwave-assisted rapid and high yielding synthesis of 2-arylamino-4-(3¢-indolyl)thiazoles involve the reaction of easily available α-tosyloxyketones with N-arylthioureas in polyethylene glycol-400 (PEG-400). In-vitro cytotoxicity study of 2-arylamino-4-(3¢-indolyl)thiazoles against a panel of human cancer cell lines revealed IC50 values in the low micromolar range. Of the fifteen synthesized arylaminothiazoles, compounds 17b, 17d, 17g and 17i-l showed significant anti-proliferative activity against the selected cancer cell lines with IC50 < 10 µM. The lead compound 17b in this series exhibited good cytotoxic activity against MCF-7 breast cancer cells with an IC50 value of 1.86 µM, which was better in comparison to doxorubicin. Furthermore, it was found that the potent compound 17b induces ROS-mediated apoptosis in MCF-7 cells in a dose-dependent manner as indicated b...
International Journal of Scientific Research, Jun 1, 2013
Biochemistry, Jan 25, 2016
The biological significance of microtubules makes them a validated target of cancer therapy. In t... more The biological significance of microtubules makes them a validated target of cancer therapy. In this study, we have utilized indole, an important pharmacological scaffold, to synthesise novel bis(indolyl)-hydrazide-hydrazone derivatives (NMK-BH compounds) and recognised NMK-BH3 as the most effective one in inhibiting A549 cell proliferation and assembly of tissue purified tubulin. Cell viability experiments showed that NMK-BH3 inhibited proliferation of human lung adenocarcinoma (A549) cells and normal human lung fibroblast (WI38) and Peripheral Blood Mononuclear Cells (PBMC) with IC50 values of ~2 µM, 48.5 µM and 62 µM , respectively. Thus, relative high cytotoxicity of NMK-BH3 towards lung carcinoma (A549) cells over normal lung fibroblast (WI38) and PBMC cells confers therapeutic advantage of reduced host toxicity. Flow cytometry, Western blot and immunofluorescence studies in A549 cell line revealed that NMK-BH3 induced G2/M arrest, mitochondrial depolarisation and apoptosis by ...
Scientific reports, Jan 29, 2016
A series of 5-(2'-indolyl)thiazoles were synthesized and evaluated for their cytotoxicity aga... more A series of 5-(2'-indolyl)thiazoles were synthesized and evaluated for their cytotoxicity against selected human cancer cell lines. The reaction of thioamides 3 with 3-tosyloxypentane-2,4-dione 4 led to in situ formation of 5-acetylthiazole 5 which upon treatment with arylhydrazines 6 in polyphosphoric acid resulted in the formation of 5-(2'-indolyl)thiazoles 2. Among the synthesized 5-(2'-indolyl)thiazoles, compounds 2d-f, and 2h exhibited encouraging anticancer activity and also selectivity towards particular cell lines (IC50 = 10-30 μM). Further studies on the SAR of compound 2e may result in good anticancer activity.
Bioorganic & Medicinal Chemistry Letters, 2015
A new series of 2-(3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;... more A new series of 2-(3&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;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;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;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;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;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;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;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;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;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;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;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;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;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;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;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;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-indolyl)-N-arylthiazole-4-carboxamides 17a-p has been designed and synthesized. Initial reaction of readily available thioamides 15 with bromopyruvic acid under refluxing conditions produced different thiazole carboxylic acids 16 which upon coupling with arylamines by using EDCI·HCl and HOBt afforded diverse arylthiazole-4-carboxamides 17a-p in 78-87% yields. Antibacterial activity evaluation against Gram-positive and Gram-negative bacterial strains led to compounds 17i-k and 17o as potent and selectively (Gram-negative) antibacterial agents. The cytotoxicity of thiazole carboxamides 17a-p was also evaluated on a panel of human cancer cell lines. Among the tested derivatives, compounds 17i (IC50=8.64μM; HEK293T) and 17l (IC50=3.41μM; HeLa) were identified as the most potent analogues of the series. Preliminary mechanism of action studies of thiazole carboxamide 17i suggested that its cytotoxicity against HeLa cells involves the induction of cell death by apoptosis.
Journal of Enzyme Inhibition and Medicinal Chemistry, 2003
A quantitative structure-activity relationship (QSAR) study is made on the inhibition of a few is... more A quantitative structure-activity relationship (QSAR) study is made on the inhibition of a few isozymes of carbonic anhydrase (CA) and some matrix metalloproteinases (MMPs), both zinc containing families of enzymes, by sulfonylated amino acid hydroxamates. For both enzymes, the inhibition potency of the hydroxamates is found to be well correlated with Kier&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;#39;s first-order valence molecular connectivity index 1chi(v) of the molecule and electrotopological state indices of some atoms. From the results, it is suggested that while hydroxamate-CA binding may involve mostly polar interactions, hydroxamate-MMP and hydroxamate-ChC (ChC: Clostridium histolyticum collagenase, another zinc enzyme related to MMPs) bindings may involve some hydrophobic interactions. Both MMPs and ChC also possess some electronic sites of exactly opposite nature to the corresponding sites in CAs. A group such as C6F5 present in the sulfonyl moiety is shown to be advantageous in both CA and MMP (also ChC) inhibitions, which is supposed to be due to the interaction of this group with Zn2+ ion present in the catalytic site of both families of enzymes.
European Journal of Medicinal Chemistry, Jul 2, 2012
A series of 2-arylamino-5-(indolyl)-1,3,4-thiadiazoles 6a-v were prepared and studied for their a... more A series of 2-arylamino-5-(indolyl)-1,3,4-thiadiazoles 6a-v were prepared and studied for their anticancer activity against selected human cancer cell lines. The reaction of indolylhydrazides 3a-h with a variety of aryl isothiocyanates 4 afforded the key intermediate thiosemicarbazides 5a-v, which upon treatment with acetyl chloride produced the 2-arylamino-5-(indolyl)-1,3,4-thiadiazoles 6a-v in good yields. Most of the synthesized compounds showed selective cytotoxicity towards human breast cancer cell line (MDA-MB-231). Of the synthesized 2-arylamino-5-(indolyl)-1,3,4-thiadiazoles, compound 6f is the most potent towards tested cancer cell lines (IC(50) = 0.15-1.18 μM).
Indian Journal of Chemistry Section B, 2009
Catalysis Lett, 1998
The use of inexpensive and recyclable phase-transfer catalysts, surfactant pillared clays, is dem... more The use of inexpensive and recyclable phase-transfer catalysts, surfactant pillared clays, is demonstrated in a simple and highly efficient synthesis of α-azidoketones from readily accessible α-tosyloxyketones and sodium azide.
Synthesis Stuttgart, 2010
Cheminform, Jan 28, 2014
AbstractAll compounds (II) possess significant antiproliferative activity against the cancer cell... more AbstractAll compounds (II) possess significant antiproliferative activity against the cancer cell lines HEK293, HeLa, LNCaP, MCF-7, PC3, and MDA-MB-231.
Journal of Chemical Research Synopses, 1997
Molecules Online, 1998
... Rajender S. Varma1, 2, Rajender Dahiya1, and Dalip Kumar1 ... AK (1993) J Chem Soc, Perkin Tr... more ... Rajender S. Varma1, 2, Rajender Dahiya1, and Dalip Kumar1 ... AK (1993) J Chem Soc, Perkin Trans 1:999; (d) Varma RS, Lamture JB, Varma M (1993) Tetrahe-dron Lett 34:3029; (e) Varma RS, Saini RK (1997) Tet-rahedron Lett 38:2623; (f) Varma RS, Meshram HM (1997 ...
Http Dx Doi Org 10 1080 00397919908086108, Sep 17, 2007
ABSTRACT
The indole ring system is the most privileged heterocycle in nature and embedded in many biologic... more The indole ring system is the most privileged heterocycle in nature and embedded in many biological systems. The demonstration of many indole containing alkaloids as leads for the new pharmaceutical agents, the recognition of the importance of essential amino acid tryptophan in human nutrition and the discovery of plant hormones served to bring about a massive search on indole chemistry. This led to report vast number of structurally diversified bio-active natural and synthetic indoles. The present review focuses on the structure-based drug design of variety of classes of synthetic indoles as potent anticancer agents. Particularly, the recent developments on natural-product inspired rational synthesis of functionalized indoles, indolylazoles and bis(indoles) and their anticancer activities are presented. This review also drawn the attention towards combretastatin-based structural class of indoles and well discussed their potentials as tubulin polymerization inhibitors.
Organic letters, Jan 5, 2017
Gold(III)-catalyzed synthesis of 14-π electron heteroaromatic thiopyrano[2,3-b]indole is reported... more Gold(III)-catalyzed synthesis of 14-π electron heteroaromatic thiopyrano[2,3-b]indole is reported using conjugated enyne tethered indole sulfides, featuring skeletal rearrangement conjoined with intramolecular hydroarylation (via C3-H functionalization of the indole core) and oxidative aromatization. Subsequent Pd-catalyzed C-C coupling resulted in a 16-π electron heteroaromatic isothiochromeno[1,8,7-bcd]indole.
Anti-cancer agents in medicinal chemistry, Jan 21, 2016
A new series of novel 2-arylamino-4-(3¢-indolyl)thiazoles have been designed as potent cytotoxic ... more A new series of novel 2-arylamino-4-(3¢-indolyl)thiazoles have been designed as potent cytotoxic agents. One-pot microwave-assisted rapid and high yielding synthesis of 2-arylamino-4-(3¢-indolyl)thiazoles involve the reaction of easily available α-tosyloxyketones with N-arylthioureas in polyethylene glycol-400 (PEG-400). In-vitro cytotoxicity study of 2-arylamino-4-(3¢-indolyl)thiazoles against a panel of human cancer cell lines revealed IC50 values in the low micromolar range. Of the fifteen synthesized arylaminothiazoles, compounds 17b, 17d, 17g and 17i-l showed significant anti-proliferative activity against the selected cancer cell lines with IC50 < 10 µM. The lead compound 17b in this series exhibited good cytotoxic activity against MCF-7 breast cancer cells with an IC50 value of 1.86 µM, which was better in comparison to doxorubicin. Furthermore, it was found that the potent compound 17b induces ROS-mediated apoptosis in MCF-7 cells in a dose-dependent manner as indicated b...
International Journal of Scientific Research, Jun 1, 2013
Biochemistry, Jan 25, 2016
The biological significance of microtubules makes them a validated target of cancer therapy. In t... more The biological significance of microtubules makes them a validated target of cancer therapy. In this study, we have utilized indole, an important pharmacological scaffold, to synthesise novel bis(indolyl)-hydrazide-hydrazone derivatives (NMK-BH compounds) and recognised NMK-BH3 as the most effective one in inhibiting A549 cell proliferation and assembly of tissue purified tubulin. Cell viability experiments showed that NMK-BH3 inhibited proliferation of human lung adenocarcinoma (A549) cells and normal human lung fibroblast (WI38) and Peripheral Blood Mononuclear Cells (PBMC) with IC50 values of ~2 µM, 48.5 µM and 62 µM , respectively. Thus, relative high cytotoxicity of NMK-BH3 towards lung carcinoma (A549) cells over normal lung fibroblast (WI38) and PBMC cells confers therapeutic advantage of reduced host toxicity. Flow cytometry, Western blot and immunofluorescence studies in A549 cell line revealed that NMK-BH3 induced G2/M arrest, mitochondrial depolarisation and apoptosis by ...
Scientific reports, Jan 29, 2016
A series of 5-(2'-indolyl)thiazoles were synthesized and evaluated for their cytotoxicity aga... more A series of 5-(2'-indolyl)thiazoles were synthesized and evaluated for their cytotoxicity against selected human cancer cell lines. The reaction of thioamides 3 with 3-tosyloxypentane-2,4-dione 4 led to in situ formation of 5-acetylthiazole 5 which upon treatment with arylhydrazines 6 in polyphosphoric acid resulted in the formation of 5-(2'-indolyl)thiazoles 2. Among the synthesized 5-(2'-indolyl)thiazoles, compounds 2d-f, and 2h exhibited encouraging anticancer activity and also selectivity towards particular cell lines (IC50 = 10-30 μM). Further studies on the SAR of compound 2e may result in good anticancer activity.
Bioorganic & Medicinal Chemistry Letters, 2015
A new series of 2-(3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;... more A new series of 2-(3&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;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;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;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;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;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;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;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;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;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;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;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;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;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;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;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;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-indolyl)-N-arylthiazole-4-carboxamides 17a-p has been designed and synthesized. Initial reaction of readily available thioamides 15 with bromopyruvic acid under refluxing conditions produced different thiazole carboxylic acids 16 which upon coupling with arylamines by using EDCI·HCl and HOBt afforded diverse arylthiazole-4-carboxamides 17a-p in 78-87% yields. Antibacterial activity evaluation against Gram-positive and Gram-negative bacterial strains led to compounds 17i-k and 17o as potent and selectively (Gram-negative) antibacterial agents. The cytotoxicity of thiazole carboxamides 17a-p was also evaluated on a panel of human cancer cell lines. Among the tested derivatives, compounds 17i (IC50=8.64μM; HEK293T) and 17l (IC50=3.41μM; HeLa) were identified as the most potent analogues of the series. Preliminary mechanism of action studies of thiazole carboxamide 17i suggested that its cytotoxicity against HeLa cells involves the induction of cell death by apoptosis.
Journal of Enzyme Inhibition and Medicinal Chemistry, 2003
A quantitative structure-activity relationship (QSAR) study is made on the inhibition of a few is... more A quantitative structure-activity relationship (QSAR) study is made on the inhibition of a few isozymes of carbonic anhydrase (CA) and some matrix metalloproteinases (MMPs), both zinc containing families of enzymes, by sulfonylated amino acid hydroxamates. For both enzymes, the inhibition potency of the hydroxamates is found to be well correlated with Kier&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;#39;s first-order valence molecular connectivity index 1chi(v) of the molecule and electrotopological state indices of some atoms. From the results, it is suggested that while hydroxamate-CA binding may involve mostly polar interactions, hydroxamate-MMP and hydroxamate-ChC (ChC: Clostridium histolyticum collagenase, another zinc enzyme related to MMPs) bindings may involve some hydrophobic interactions. Both MMPs and ChC also possess some electronic sites of exactly opposite nature to the corresponding sites in CAs. A group such as C6F5 present in the sulfonyl moiety is shown to be advantageous in both CA and MMP (also ChC) inhibitions, which is supposed to be due to the interaction of this group with Zn2+ ion present in the catalytic site of both families of enzymes.
European Journal of Medicinal Chemistry, Jul 2, 2012
A series of 2-arylamino-5-(indolyl)-1,3,4-thiadiazoles 6a-v were prepared and studied for their a... more A series of 2-arylamino-5-(indolyl)-1,3,4-thiadiazoles 6a-v were prepared and studied for their anticancer activity against selected human cancer cell lines. The reaction of indolylhydrazides 3a-h with a variety of aryl isothiocyanates 4 afforded the key intermediate thiosemicarbazides 5a-v, which upon treatment with acetyl chloride produced the 2-arylamino-5-(indolyl)-1,3,4-thiadiazoles 6a-v in good yields. Most of the synthesized compounds showed selective cytotoxicity towards human breast cancer cell line (MDA-MB-231). Of the synthesized 2-arylamino-5-(indolyl)-1,3,4-thiadiazoles, compound 6f is the most potent towards tested cancer cell lines (IC(50) = 0.15-1.18 μM).
Indian Journal of Chemistry Section B, 2009
Catalysis Lett, 1998
The use of inexpensive and recyclable phase-transfer catalysts, surfactant pillared clays, is dem... more The use of inexpensive and recyclable phase-transfer catalysts, surfactant pillared clays, is demonstrated in a simple and highly efficient synthesis of α-azidoketones from readily accessible α-tosyloxyketones and sodium azide.
Synthesis Stuttgart, 2010
Cheminform, Jan 28, 2014
AbstractAll compounds (II) possess significant antiproliferative activity against the cancer cell... more AbstractAll compounds (II) possess significant antiproliferative activity against the cancer cell lines HEK293, HeLa, LNCaP, MCF-7, PC3, and MDA-MB-231.
Journal of Chemical Research Synopses, 1997
Molecules Online, 1998
... Rajender S. Varma1, 2, Rajender Dahiya1, and Dalip Kumar1 ... AK (1993) J Chem Soc, Perkin Tr... more ... Rajender S. Varma1, 2, Rajender Dahiya1, and Dalip Kumar1 ... AK (1993) J Chem Soc, Perkin Trans 1:999; (d) Varma RS, Lamture JB, Varma M (1993) Tetrahe-dron Lett 34:3029; (e) Varma RS, Saini RK (1997) Tet-rahedron Lett 38:2623; (f) Varma RS, Meshram HM (1997 ...
Http Dx Doi Org 10 1080 00397919908086108, Sep 17, 2007
ABSTRACT
The indole ring system is the most privileged heterocycle in nature and embedded in many biologic... more The indole ring system is the most privileged heterocycle in nature and embedded in many biological systems. The demonstration of many indole containing alkaloids as leads for the new pharmaceutical agents, the recognition of the importance of essential amino acid tryptophan in human nutrition and the discovery of plant hormones served to bring about a massive search on indole chemistry. This led to report vast number of structurally diversified bio-active natural and synthetic indoles. The present review focuses on the structure-based drug design of variety of classes of synthetic indoles as potent anticancer agents. Particularly, the recent developments on natural-product inspired rational synthesis of functionalized indoles, indolylazoles and bis(indoles) and their anticancer activities are presented. This review also drawn the attention towards combretastatin-based structural class of indoles and well discussed their potentials as tubulin polymerization inhibitors.