Kanchan Hajela - Academia.edu (original) (raw)
Papers by Kanchan Hajela
Chemistry (Weinheim an der Bergstrasse, Germany), Jan 14, 2015
A highly efficient synthesis of phenanthridine/benzoxazine-fused quinazolinones by ligand-free pa... more A highly efficient synthesis of phenanthridine/benzoxazine-fused quinazolinones by ligand-free palladium-catalyzed intramolecular C-H bond activation under mild conditions has been developed. The C-C coupling provides the corresponding N-fused polycyclic heterocycles in good to excellent yields and with wide functional group tolerance.
Synthetic Communications
An efficient synthesis of 3,6-disubstituted-4-aroyl-2-pyrones in a single-step reaction through M... more An efficient synthesis of 3,6-disubstituted-4-aroyl-2-pyrones in a single-step reaction through Michael addition of 1,2-diaroylacetylenes with active methylene compounds in the presence of NaH in dimethylsulfoxide at room temperature is reported. The structures have been confirmed by spectral data analyses.
Org. Biomol. Chem., 2015
DNA ligases are critical components for DNA metabolism in all organisms. NAD(+)-dependent DNA lig... more DNA ligases are critical components for DNA metabolism in all organisms. NAD(+)-dependent DNA ligases (LigA) found exclusively in bacteria and certain entomopoxviruses are drawing increasing attention as therapeutic targets as they differ in their cofactor requirement from ATP-dependent eukaryotic homologs. Due to the similarities in the cofactor binding sites of the two classes of DNA ligases, it is necessary to find determinants that can distinguish between them for the exploitation of LigA as an anti-bacterial target. In the present endeavour, we have synthesized and evaluated a series of tricyclic dihydrobenzoxazepine and tetracyclic indole derivatives for their ability to distinguish between bacterial and human DNA ligases. The in vivo inhibition assays that employed LigA deficient E. coli GR501 and S. typhimurium LT2 bacterial strains, rescued by ATP-dependent T4 DNA ligase or Mycobacterium tuberculosis NAD(+)-dependent DNA ligase (Mtb LigA), respectively, showed that the compounds can specifically inhibit bacterial LigA. The in vitro enzyme inhibition assays using purified MtbLigA, human DNA ligase I & T4 DNA ligase showed specific inhibition of MtbLigA at low micromolar range. Our results demonstrate that tricyclic dihydrobenzoxazepine and tetracyclic indole derivatives can distinguish between bacterial and human DNA ligases by ∼5-folds. In silico docking and enzyme inhibition assays identified that the compounds bind to the cofactor binding site and compete with the cofactor. Ethidium bromide displacement and gel-shift assays showed that the inhibitors do not exhibit any unwanted general interactions with the substrate DNA. These results set the stage for the detailed exploration of this compound class for development as antibacterials.
ChemInform, 2004
Facile Synthesis of 2-Arylbenzo[b]furans Through Unusual Acid Catalyzed 1,2-Elimination. ... For ... more Facile Synthesis of 2-Arylbenzo[b]furans Through Unusual Acid Catalyzed 1,2-Elimination. ... For Abstract see ChemInform Abstract in Full Text. ... Mechanistical aspects of the transformation of (III) to (IV) are discussed. The structure of compound (III) is determined by X-ray analysis.
Tetrahedron Letters, 2006
Several 1,5-diketones have been prepared in good to excellent yields by versatile conjugate addit... more Several 1,5-diketones have been prepared in good to excellent yields by versatile conjugate addition of nucleophiles such as cyclic or acyclic ketones, amines and thiols to a,b-unsaturated enones and alkynones, in the presence of catalytic amounts of 10% aq NaOH, TBAI and DMSO at ambient temperature. The choice of solvent and phase-transfer catalyst played a critical role in improving the reaction rate and yields of the products.
Steroids, 2013
In an endeavor to develop novel and improved selective estrogen receptor modulators as anti-breas... more In an endeavor to develop novel and improved selective estrogen receptor modulators as anti-breast cancer agents, the benzopyran compounds have been synthesized and identified which act as potent anti-estrogen at uterine level. The present study evaluates the anti-tumor activity of 2-[piperidinoethoxyphenyl]-3-phenyl-2H-benzo(b)pyran (CDRI-85/287) and explores the mechanism of action with a view to describe its potential to inhibit proliferation in ER-positive breast cancer cells MCF-7 and T47D. The compound decreased the expression of ERa while increased the expression of ERb thereby altering ERa/ERb ratio in both cell lines. Although the compound showed low binding affinity to ERs, it acted as ERa antagonist and ERb agonist in decreasing ERE-or AP-1-mediated transcriptional activation in these cells. Transactivation studies in ERa/b-transfected MDA-MB231 cells suggested that at cyclin D1 promoter, compound antagonized the action of ERa-mediated E 2 response while acted as estrogen agonist via ERb. Further, the compound led to decreased expression of ERa-dependent proliferation markers and ERb-dependent cell cycle progression markers. The expression of cell cycle inhibitory protein p21 was increased leading to G2/M phase arrest. In parallel, compound also interfered with EGFR activation, caused inhibition of PI-3-K/Akt pathway and subsequent induction of apoptosis via intrinsic pathway. A significant reduction in tumor mass and volume was observed in 85/287-treated mice bearing MCF-7 xenograft. We conclude that compound 85/287 exhibits significant anti-tumor activity via modulation of genomic as well as non-genomic mechanisms involved in cellular growth and arrested the cells in G2 phase in both MCF-7 and T47D breast cancer cells. Study suggests that CDRI-85/287 may have therapeutic potential in ER-positive breast cancer.
New Journal of Chemistry, 2014
ABSTRACT A metal-free one-pot approach to the diversity oriented synthesis of N-heterocycles, 1,2... more ABSTRACT A metal-free one-pot approach to the diversity oriented synthesis of N-heterocycles, 1,2,4- oxadiazoles and 2,6 disubstituted pyrimidin-4-ones is described via carboxamidation of amidines with aryl carboxylic acids and aryl propargylic acids. The reactions occur at room temperature forming N-acylamidines which undergo tandem nucleophilic addition / deamination / intramolecular cyclisation to give the corresponding heterocyclic compounds in good to excellent yields. This one pot approach has led to the successful synthesis of drug lead molecule, ataluren, (3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl) benzoic acid in two steps.
Journal of Biological Chemistry, 2005
DNA ligases utilize either ATP or NAD ؉ as cofactors to catalyze the formation of phosphodiester ... more DNA ligases utilize either ATP or NAD ؉ as cofactors to catalyze the formation of phosphodiester bonds in nicked DNA. Those utilizing NAD ؉ are attractive drug targets because of the unique cofactor requirement for ligase activity. We report here the crystal structure of the adenylation domain of the Mycobacterium tuberculosis NAD ؉ -dependent ligase with bound AMP. The adenosine nucleoside moiety of AMP adopts a syn-conformation. The structure also captures a new spatial disposition between the two subdomains of the adenylation domain. Based on the crystal structure and an in-house compound library, we have identified a novel class of inhibitors for the enzyme using in silico docking calculations. The glycosyl ureide-based inhibitors were able to distinguish between NAD ؉ -and ATP-dependent ligases as evidenced by in vitro assays using T4 ligase and human DNA ligase I. Moreover, assays involving an Escherichia coli strain harboring a temperature-sensitive ligase mutant and a ligase-deficient Salmonella typhimurium strain suggested that the bactericidal activity of the inhibitors is due to inhibition of the essential ligase enzyme. The results can be used as the basis for rational design of novel antibacterial agents. 1 The abbreviations used are: TfiLigA, T. filiformis LigA; EfaLigA, E. faecalis LigA; MtuLigA, M. tuberculosis LigA; MICs, minimum inhibitory concentrations; EcoLigA, E. coli LigA.
Molecular and cellular endocrinology, Jan 2, 2012
The present study was undertaken to explore the mechanism of anti-proliferative action of benzopy... more The present study was undertaken to explore the mechanism of anti-proliferative action of benzopyran compound D1 (2-[piperidinoethoxyphenyl]-3-phenyl-2H-benzopyran) and its hydroxy-(D2) and methoxy-(D3) derivatives in Ishikawa and human primary endometrial adenocarcinoma cells.
Gynecologic Oncology, 2013
The aim of the present study was to investigate the effect of non-steroidal, pure antiestrogenic ... more The aim of the present study was to investigate the effect of non-steroidal, pure antiestrogenic benzopyran derivative i.e., 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran (K-1) on the growth of human endometrial cancer cells in vivo and in vitro and to elucidate its mechanism of action. Cell proliferation was assayed by measuring the incorporation of 5'-bromo-2'-deoxyuridine in Ishikawa and primary endometrial cancer cells. The expression of proliferation and apoptotic markers was analyzed by immunoblotting. The effect of K-1 on GPR30-regulated proteins was analyzed by ELISA and by immunoblotting. Nude mice bearing subcutaneous implanted-Ishikawa tumors, were treated for 14days with K-1 (200μg/kg body weight/day/orally). The proliferation markers, GPR30-regulated proteins and apoptotic markers were analyzed by immunoblotting in tumor xenograft. The apoptotic effect of compound K-1 was determined by TUNEL assay. Compound K-1 inhibited proliferation of endometrial adenocarcinoma cells and decreased the expression of proliferation markers. It caused apoptosis by increasing the expression of apoptotic markers (NOXA, PUMAα) and reducing the expression of p-CREB and BclxL. Compound interfered with GPR30-regulated-EGFR activation, decreased p-ERK, p-c-jun, c-fos, cyclinD1 and c-myc expression. Treatment of tumor-bearing mice with K-1 resulted in a significant decrease in tumor volume and weight. Decreased expression of p-ERK and its downstream molecules and increased expression of apoptotic markers were observed in tumor in K-1 treated animals. Findings suggest the potent inhibitory effect of compound K-1 on endometrial cancer cellular growth (in-vitro) and on tumor size (in-vivo) which is mediated at least, in part, by interference with GPR30-signaling.
Arzneimittelforschung, 2011
1,2-Bis(4-substituted phenyl)-2-methyl ethanone (2,4-dinitrophenyl)hydrazones and 1-naphthyl-1-(4... more 1,2-Bis(4-substituted phenyl)-2-methyl ethanone (2,4-dinitrophenyl)hydrazones and 1-naphthyl-1-(4-substituted phenyl)-methanone (2,4-dinitrophenyl)hydrazones have been synthesized and evaluated for their anti-implantation, uterotrophic, antiuterotrophic, anticancer and antimicrobial activities. Diphenolic hydrazone (compound 6) showed maximum uterotrophic inhibition of 70%, whereas compound 20 exhibited cytotoxicity in the range of 50-70% against MCF-7 and ZR-75-1 human malignant breast cell lines.
![Research paper thumbnail of Resolution, molecular structure and biological activities of the d- and l-enantiomers of potent anti-implantation agent, dl-2-[4-(2-Piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran](https://attachments.academia-assets.com/49478559/thumbnails/1.jpg)
](Bioorganic & Medicinal Chemistry, 1999
AbstractÐCompound 1 (dl-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran, CDRI 85/287) a... more AbstractÐCompound 1 (dl-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran, CDRI 85/287) a potent anti-estrogen and anti-implantation agent has been successfully resolved into its pure d-and l-enantiomers. Biological studies showed l-enantiomer to be the active form, exhibiting a ®vefold higher receptor anity for the rat uterine cytosolic estrogen receptor, 100% contraceptive ecacy at 1.3 mg/kg dose in single day schedule and 89% inhibition of estradiol induced increase of uterine weight at its contraceptive dose. The absolute stereochemistry determined by X-ray crystallographic analysis showed that the l-enantiomer has 2R con®guration at its asymmetric centre. #
Bioorganic & Medicinal Chemistry, 2009
A series of 3,4,6-triaryl-2-pyranones, new class of anti-breast cancer agents, have been synthesi... more A series of 3,4,6-triaryl-2-pyranones, new class of anti-breast cancer agents, have been synthesized as a structural variants of cyclic triphenylethylenes by replacing the fused benzene ring with pendant phenyl ring to mimic the phenolic A ring of estradiol. Nine of these newly synthesized pyranones exhibited significant anti-proliferative activity in both ER+ve and ERÀve breast cancer cell lines. Four active non-cytotoxic compounds 5c, 5d, 5g and 5h showed specific and selective cytotoxicity and two compounds 5d and 5h induced significant DNA fragmentation in both MCF-7 and MDA-MB-231 cell lines. Based on RBA studies, the molecules probably act in an ER-independent mechanism. The involved pathway was observed as caspase-dependant apoptosis in MCF-7 cells. However, the particular caspases involved and the possible cellular target through which this series of compounds mediate cell death are not known.
Archiv der Pharmazie, 1983
... SS Dixit and SS Parmar, J. Pharm. Sci. 62,613 (1973). 6 AK Sen Gupta and HK Misra, Indian J. ... more ... SS Dixit and SS Parmar, J. Pharm. Sci. 62,613 (1973). 6 AK Sen Gupta and HK Misra, Indian J. Chem. 173, 185 (1979). 7 AK Sen Gupta and HK Misra, Indian J. Chem. 183, 381 (1979). 8 AK Sen Gupta and HK Misra, J. Pharm. Sci., 69, 1313 (1982). 9 PN Bhargava and MR ...
Chemistry (Weinheim an der Bergstrasse, Germany), Jan 14, 2015
A highly efficient synthesis of phenanthridine/benzoxazine-fused quinazolinones by ligand-free pa... more A highly efficient synthesis of phenanthridine/benzoxazine-fused quinazolinones by ligand-free palladium-catalyzed intramolecular C-H bond activation under mild conditions has been developed. The C-C coupling provides the corresponding N-fused polycyclic heterocycles in good to excellent yields and with wide functional group tolerance.
Synthetic Communications
An efficient synthesis of 3,6-disubstituted-4-aroyl-2-pyrones in a single-step reaction through M... more An efficient synthesis of 3,6-disubstituted-4-aroyl-2-pyrones in a single-step reaction through Michael addition of 1,2-diaroylacetylenes with active methylene compounds in the presence of NaH in dimethylsulfoxide at room temperature is reported. The structures have been confirmed by spectral data analyses.
Org. Biomol. Chem., 2015
DNA ligases are critical components for DNA metabolism in all organisms. NAD(+)-dependent DNA lig... more DNA ligases are critical components for DNA metabolism in all organisms. NAD(+)-dependent DNA ligases (LigA) found exclusively in bacteria and certain entomopoxviruses are drawing increasing attention as therapeutic targets as they differ in their cofactor requirement from ATP-dependent eukaryotic homologs. Due to the similarities in the cofactor binding sites of the two classes of DNA ligases, it is necessary to find determinants that can distinguish between them for the exploitation of LigA as an anti-bacterial target. In the present endeavour, we have synthesized and evaluated a series of tricyclic dihydrobenzoxazepine and tetracyclic indole derivatives for their ability to distinguish between bacterial and human DNA ligases. The in vivo inhibition assays that employed LigA deficient E. coli GR501 and S. typhimurium LT2 bacterial strains, rescued by ATP-dependent T4 DNA ligase or Mycobacterium tuberculosis NAD(+)-dependent DNA ligase (Mtb LigA), respectively, showed that the compounds can specifically inhibit bacterial LigA. The in vitro enzyme inhibition assays using purified MtbLigA, human DNA ligase I & T4 DNA ligase showed specific inhibition of MtbLigA at low micromolar range. Our results demonstrate that tricyclic dihydrobenzoxazepine and tetracyclic indole derivatives can distinguish between bacterial and human DNA ligases by ∼5-folds. In silico docking and enzyme inhibition assays identified that the compounds bind to the cofactor binding site and compete with the cofactor. Ethidium bromide displacement and gel-shift assays showed that the inhibitors do not exhibit any unwanted general interactions with the substrate DNA. These results set the stage for the detailed exploration of this compound class for development as antibacterials.
ChemInform, 2004
Facile Synthesis of 2-Arylbenzo[b]furans Through Unusual Acid Catalyzed 1,2-Elimination. ... For ... more Facile Synthesis of 2-Arylbenzo[b]furans Through Unusual Acid Catalyzed 1,2-Elimination. ... For Abstract see ChemInform Abstract in Full Text. ... Mechanistical aspects of the transformation of (III) to (IV) are discussed. The structure of compound (III) is determined by X-ray analysis.
Tetrahedron Letters, 2006
Several 1,5-diketones have been prepared in good to excellent yields by versatile conjugate addit... more Several 1,5-diketones have been prepared in good to excellent yields by versatile conjugate addition of nucleophiles such as cyclic or acyclic ketones, amines and thiols to a,b-unsaturated enones and alkynones, in the presence of catalytic amounts of 10% aq NaOH, TBAI and DMSO at ambient temperature. The choice of solvent and phase-transfer catalyst played a critical role in improving the reaction rate and yields of the products.
Steroids, 2013
In an endeavor to develop novel and improved selective estrogen receptor modulators as anti-breas... more In an endeavor to develop novel and improved selective estrogen receptor modulators as anti-breast cancer agents, the benzopyran compounds have been synthesized and identified which act as potent anti-estrogen at uterine level. The present study evaluates the anti-tumor activity of 2-[piperidinoethoxyphenyl]-3-phenyl-2H-benzo(b)pyran (CDRI-85/287) and explores the mechanism of action with a view to describe its potential to inhibit proliferation in ER-positive breast cancer cells MCF-7 and T47D. The compound decreased the expression of ERa while increased the expression of ERb thereby altering ERa/ERb ratio in both cell lines. Although the compound showed low binding affinity to ERs, it acted as ERa antagonist and ERb agonist in decreasing ERE-or AP-1-mediated transcriptional activation in these cells. Transactivation studies in ERa/b-transfected MDA-MB231 cells suggested that at cyclin D1 promoter, compound antagonized the action of ERa-mediated E 2 response while acted as estrogen agonist via ERb. Further, the compound led to decreased expression of ERa-dependent proliferation markers and ERb-dependent cell cycle progression markers. The expression of cell cycle inhibitory protein p21 was increased leading to G2/M phase arrest. In parallel, compound also interfered with EGFR activation, caused inhibition of PI-3-K/Akt pathway and subsequent induction of apoptosis via intrinsic pathway. A significant reduction in tumor mass and volume was observed in 85/287-treated mice bearing MCF-7 xenograft. We conclude that compound 85/287 exhibits significant anti-tumor activity via modulation of genomic as well as non-genomic mechanisms involved in cellular growth and arrested the cells in G2 phase in both MCF-7 and T47D breast cancer cells. Study suggests that CDRI-85/287 may have therapeutic potential in ER-positive breast cancer.
New Journal of Chemistry, 2014
ABSTRACT A metal-free one-pot approach to the diversity oriented synthesis of N-heterocycles, 1,2... more ABSTRACT A metal-free one-pot approach to the diversity oriented synthesis of N-heterocycles, 1,2,4- oxadiazoles and 2,6 disubstituted pyrimidin-4-ones is described via carboxamidation of amidines with aryl carboxylic acids and aryl propargylic acids. The reactions occur at room temperature forming N-acylamidines which undergo tandem nucleophilic addition / deamination / intramolecular cyclisation to give the corresponding heterocyclic compounds in good to excellent yields. This one pot approach has led to the successful synthesis of drug lead molecule, ataluren, (3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl) benzoic acid in two steps.
Journal of Biological Chemistry, 2005
DNA ligases utilize either ATP or NAD ؉ as cofactors to catalyze the formation of phosphodiester ... more DNA ligases utilize either ATP or NAD ؉ as cofactors to catalyze the formation of phosphodiester bonds in nicked DNA. Those utilizing NAD ؉ are attractive drug targets because of the unique cofactor requirement for ligase activity. We report here the crystal structure of the adenylation domain of the Mycobacterium tuberculosis NAD ؉ -dependent ligase with bound AMP. The adenosine nucleoside moiety of AMP adopts a syn-conformation. The structure also captures a new spatial disposition between the two subdomains of the adenylation domain. Based on the crystal structure and an in-house compound library, we have identified a novel class of inhibitors for the enzyme using in silico docking calculations. The glycosyl ureide-based inhibitors were able to distinguish between NAD ؉ -and ATP-dependent ligases as evidenced by in vitro assays using T4 ligase and human DNA ligase I. Moreover, assays involving an Escherichia coli strain harboring a temperature-sensitive ligase mutant and a ligase-deficient Salmonella typhimurium strain suggested that the bactericidal activity of the inhibitors is due to inhibition of the essential ligase enzyme. The results can be used as the basis for rational design of novel antibacterial agents. 1 The abbreviations used are: TfiLigA, T. filiformis LigA; EfaLigA, E. faecalis LigA; MtuLigA, M. tuberculosis LigA; MICs, minimum inhibitory concentrations; EcoLigA, E. coli LigA.
Molecular and cellular endocrinology, Jan 2, 2012
The present study was undertaken to explore the mechanism of anti-proliferative action of benzopy... more The present study was undertaken to explore the mechanism of anti-proliferative action of benzopyran compound D1 (2-[piperidinoethoxyphenyl]-3-phenyl-2H-benzopyran) and its hydroxy-(D2) and methoxy-(D3) derivatives in Ishikawa and human primary endometrial adenocarcinoma cells.
Gynecologic Oncology, 2013
The aim of the present study was to investigate the effect of non-steroidal, pure antiestrogenic ... more The aim of the present study was to investigate the effect of non-steroidal, pure antiestrogenic benzopyran derivative i.e., 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran (K-1) on the growth of human endometrial cancer cells in vivo and in vitro and to elucidate its mechanism of action. Cell proliferation was assayed by measuring the incorporation of 5'-bromo-2'-deoxyuridine in Ishikawa and primary endometrial cancer cells. The expression of proliferation and apoptotic markers was analyzed by immunoblotting. The effect of K-1 on GPR30-regulated proteins was analyzed by ELISA and by immunoblotting. Nude mice bearing subcutaneous implanted-Ishikawa tumors, were treated for 14days with K-1 (200μg/kg body weight/day/orally). The proliferation markers, GPR30-regulated proteins and apoptotic markers were analyzed by immunoblotting in tumor xenograft. The apoptotic effect of compound K-1 was determined by TUNEL assay. Compound K-1 inhibited proliferation of endometrial adenocarcinoma cells and decreased the expression of proliferation markers. It caused apoptosis by increasing the expression of apoptotic markers (NOXA, PUMAα) and reducing the expression of p-CREB and BclxL. Compound interfered with GPR30-regulated-EGFR activation, decreased p-ERK, p-c-jun, c-fos, cyclinD1 and c-myc expression. Treatment of tumor-bearing mice with K-1 resulted in a significant decrease in tumor volume and weight. Decreased expression of p-ERK and its downstream molecules and increased expression of apoptotic markers were observed in tumor in K-1 treated animals. Findings suggest the potent inhibitory effect of compound K-1 on endometrial cancer cellular growth (in-vitro) and on tumor size (in-vivo) which is mediated at least, in part, by interference with GPR30-signaling.
Arzneimittelforschung, 2011
1,2-Bis(4-substituted phenyl)-2-methyl ethanone (2,4-dinitrophenyl)hydrazones and 1-naphthyl-1-(4... more 1,2-Bis(4-substituted phenyl)-2-methyl ethanone (2,4-dinitrophenyl)hydrazones and 1-naphthyl-1-(4-substituted phenyl)-methanone (2,4-dinitrophenyl)hydrazones have been synthesized and evaluated for their anti-implantation, uterotrophic, antiuterotrophic, anticancer and antimicrobial activities. Diphenolic hydrazone (compound 6) showed maximum uterotrophic inhibition of 70%, whereas compound 20 exhibited cytotoxicity in the range of 50-70% against MCF-7 and ZR-75-1 human malignant breast cell lines.
Bioorganic & Medicinal Chemistry, 1999
AbstractÐCompound 1 (dl-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran, CDRI 85/287) a... more AbstractÐCompound 1 (dl-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran, CDRI 85/287) a potent anti-estrogen and anti-implantation agent has been successfully resolved into its pure d-and l-enantiomers. Biological studies showed l-enantiomer to be the active form, exhibiting a ®vefold higher receptor anity for the rat uterine cytosolic estrogen receptor, 100% contraceptive ecacy at 1.3 mg/kg dose in single day schedule and 89% inhibition of estradiol induced increase of uterine weight at its contraceptive dose. The absolute stereochemistry determined by X-ray crystallographic analysis showed that the l-enantiomer has 2R con®guration at its asymmetric centre. #
Bioorganic & Medicinal Chemistry, 2009
A series of 3,4,6-triaryl-2-pyranones, new class of anti-breast cancer agents, have been synthesi... more A series of 3,4,6-triaryl-2-pyranones, new class of anti-breast cancer agents, have been synthesized as a structural variants of cyclic triphenylethylenes by replacing the fused benzene ring with pendant phenyl ring to mimic the phenolic A ring of estradiol. Nine of these newly synthesized pyranones exhibited significant anti-proliferative activity in both ER+ve and ERÀve breast cancer cell lines. Four active non-cytotoxic compounds 5c, 5d, 5g and 5h showed specific and selective cytotoxicity and two compounds 5d and 5h induced significant DNA fragmentation in both MCF-7 and MDA-MB-231 cell lines. Based on RBA studies, the molecules probably act in an ER-independent mechanism. The involved pathway was observed as caspase-dependant apoptosis in MCF-7 cells. However, the particular caspases involved and the possible cellular target through which this series of compounds mediate cell death are not known.
Archiv der Pharmazie, 1983
... SS Dixit and SS Parmar, J. Pharm. Sci. 62,613 (1973). 6 AK Sen Gupta and HK Misra, Indian J. ... more ... SS Dixit and SS Parmar, J. Pharm. Sci. 62,613 (1973). 6 AK Sen Gupta and HK Misra, Indian J. Chem. 173, 185 (1979). 7 AK Sen Gupta and HK Misra, Indian J. Chem. 183, 381 (1979). 8 AK Sen Gupta and HK Misra, J. Pharm. Sci., 69, 1313 (1982). 9 PN Bhargava and MR ...
![Research paper thumbnail of Tandem C‑2 Functionalization−Intramolecular Azide−Alkyne 1,3‑Dipolar Cycloaddition Reaction: A Convenient Route to Highly Diversified 9H‑Benzo[b]pyrrolo[1,2‑g][1,2,3]triazolo[1,5‑d][1,4]diazepines](https://attachments.academia-assets.com/39973281/thumbnails/1.jpg)
](An efficient diversity-oriented synthetic approach to annulated 9H-benzo[b]pyrrolo[1,2-g][1,2,3]t... more An efficient diversity-oriented synthetic approach to annulated 9H-benzo[b]pyrrolo[1,2-g][1,2,3]triazolo[1,5-d][1,4]diazepines has been developed using a Sc(OTf) 3 -catalyzed two-component tandem C-2 functionalization−intramolecular azide−alkyne 1,3-dipolar cycloaddition reaction. The reaction shows high substrate tolerance and provides a library of fused heterocycles that may lead to novel biologically active compounds or drug lead molecules.
![Research paper thumbnail of Synthesis of targeted dibenzo[b,f]thiepines and dibenzo[b,f]oxepines as potential lead molecules with promising anti-breast cancer activity](https://attachments.academia-assets.com/39973374/thumbnails/1.jpg)
](A targeted library of substituted dibenzo[b,f]thiepines and dibenzo [b,f]oxepines (prototypes I, ... more A targeted library of substituted dibenzo[b,f]thiepines and dibenzo [b,f]oxepines (prototypes I, II and III), and structurally analogous to tamoxifen have been synthesized as a new class of anti-breast cancer agents. All the prototype molecules exhibited potential antiproliferative activity against ER þ ve and ERve breast cancer cell lines. Dibenzo[b,f]thiepine prototypes were found to be more active. Of all the compound tested, 14b exhibited potent in-vitro antiproliferative activity at 1.33 mM and 5 mM concentration in MCF-7 and MDA-MB-231 cell lines and was devoid of any cytotoxicity in normal HEK cells even at 50 mM. Cell cycle analysis showed that the compound 14b inhibited cell proliferation due to G0/G1 arrest in MCF-7 cells. Annexin-V FITC and PI staining experiments confirmed that the cell inhibition was primarily due to apoptosis and not by necrosis, which was also supported by LDH release assay experiment. Molecular docking studies showed better binding interaction of the new dibenzo[b,f]thiepine analogue 14b with the estrogen receptor (ER) as compared to 4-hydroxy-tamoxifen and this enhanced binding might be responsible for its estrogen antagonistic activity that induces cell cycle arrest, apoptosis and inhibition of breast cancer cells.
in Wiley Online Library (wileyonlinelibrary.com).
![Research paper thumbnail of A highly efficient ultrasound-promoted synthesis of 2,3-disubstituted benzo[b]furans via intramolecular C-C bond formation in ionic liquid[bmim]BF4 at room temperature.](https://attachments.academia-assets.com/39972406/thumbnails/1.jpg)
](A highly efficient ultrasound-promoted synthesis of 2,3disubstituted benzo [b]furans via intramol... more A highly efficient ultrasound-promoted synthesis of 2,3disubstituted benzo [b]furans via intramolecular C-C bond formation in ionic liquid[bmim]BF 4 at room temperature3
A rapid and chemoselective method for the N-formylation of structurally diverse amines with formi... more A rapid and chemoselective method for the N-formylation of structurally diverse amines with formic acid using silica supported perchloric acid (HClO 4 -SiO 2 ) at room temperature and under solvent-free conditions has been developed. The catalyst was found to be compatible with different functional groups and the formylation proceeded smoothly with amines bearing electron withdrawing as well as electron donating substituents.