Girdhar S Deora | Monash University (original) (raw)
Uploads
Papers by Girdhar S Deora
Letters in Drug Design Amp Discovery, 2011
Medicinal Chemistry Research
Letters in Drug Design & Discovery, 2011
... Moorthy 1,4 , Hoyun Lee 2,3 , Kapendra Sahu 1 , Girdhar Singh Deora 1 and Piyush Trivedi* ,1 ... more ... Moorthy 1,4 , Hoyun Lee 2,3 , Kapendra Sahu 1 , Girdhar Singh Deora 1 and Piyush Trivedi* ,1 1School of Pharmaceutical Sciences, Rajiv Gandhi Technical University, Airport Bypass Road, Gandhi Nagar, Bhopal-462036 (MP), India 2Tumour Biology Group, Northeastern ...
Tetrahedron Letters, 2013
European Journal of Medicinal Chemistry, 2014
The link between PDE4 and apoptosis prompted us to design and synthesize for the first time a ser... more The link between PDE4 and apoptosis prompted us to design and synthesize for the first time a series of novel 1-thienyl pyrroloquinoxalines as potential PDE4 inhibitors/apoptotic agents. A ligand-free Pd-catalyzed C-N cross-coupling/cyclization strategy has been developed for the rapid and milder access to this class of compounds some of which showed interesting pharmacological properties when tested in vitro and in zebrafish embryos.
Tetrahedron Letters, 2014
ABSTRACT The linkage between dopamine D2 receptors and PDE activity via cAMP prompted us to desig... more ABSTRACT The linkage between dopamine D2 receptors and PDE activity via cAMP prompted us to design a series of novel N-(3-arylprop-2-ynyl)substituted olanzapine derivatives as potential inhibitors of PDE4B. The target compounds were conveniently prepared by using a simple and inexpensive method involving Pd/C-mediated C-C bond forming reaction under Sonogashira conditions. A number of compounds were synthesized by using this strategy in good yields. Some of the compounds showed promising inhibition of PDE4B when tested in vitro that was supported by the docking studies.
Tetrahedron Letters, 2012
ABSTRACT AgNO3 facilitated the intramolecular ring closure of o-(1-alkynyl)benzenesulfonamides vi... more ABSTRACT AgNO3 facilitated the intramolecular ring closure of o-(1-alkynyl)benzenesulfonamides via a regioselective C-N bond forming reaction leading to the formation of 3-substituted benzothiazine derivatives. A number of compounds were prepared in good yields by using this inexpensive and safe methodology. All the compounds synthesized were evaluated for their cyclooxygenase (COX) inhibiting properties in vitro. A number of compounds that do not contain an enolic hydroxyl group showed selectivities toward COX-2 over COX-1 inhibition. This was further supported by the predictive binding mode of two compounds with COX-1 and -2 proteins through molecular docking studies.
Synthetic Communications, 2014
ABSTRACT A simple and inexpensive synthesis of novel 2-(3-oxo-3-arylpropyl)-2,3-dihydro-1H-inden-... more ABSTRACT A simple and inexpensive synthesis of novel 2-(3-oxo-3-arylpropyl)-2,3-dihydro-1H-inden-1-one derivatives has been achieved via Pd/C-mediated arylation followed by I2-mediated regioselectivehydration of 2-(prop-2-ynyl)-2,3-dihydro-1H-inden-1-ones. A wide variety of 3-aryl substituted 2-propynyl indanone derivatives were conveniently prepared by using 10% Pd/C-PPh3-CuI as a catalyst system some of which were used to prepare the corresponding ketones via alkyne hydration in the presence of catalytic I2. In an in vitro study a representative compound showed inhibition of PDE4B (phosphodiesterase type 4B) and binding with this protein in silico.
Organic & Biomolecular Chemistry, 2013
A series of 1,3-disubstituted pyrrolo[2,3-b]quinoxalines has been designed for the potential inhi... more A series of 1,3-disubstituted pyrrolo[2,3-b]quinoxalines has been designed for the potential inhibition of PDE4 without inhibiting luciferase. A ligand/PTC (phase transfer catalyst) free intramolecular Heck cyclization strategy was used to prepare these compounds, some of which showed significant inhibition of PDE4B (IC50≈ 5-14 μM) and growth inhibition of oral cancer cells (CAL 27) but not inhibition of luciferase in vitro. They also showed acceptable safety profiles but no apoptosis in zebrafish embryos.
Organic & Biomolecular Chemistry, 2013
A series of functionalized phenyl oxazole derivatives was designed, synthesized and screened in v... more A series of functionalized phenyl oxazole derivatives was designed, synthesized and screened in vitro for their activities against LSD1 and for effects on viability of cervical and breast cancer cells, and in vivo for effects using zebrafish embryos. These compounds are likely to act via multiple epigenetic mechanisms specific to cancer cells including LSD1 inhibition.
Organic & Biomolecular Chemistry, 2013
A new strategy for converting antipsychotic drug olanzapine into PDE4 inhibitors is described via... more A new strategy for converting antipsychotic drug olanzapine into PDE4 inhibitors is described via the design and Pd/C mediated synthesis of novel N-indolylmethyl olanzapine derivatives. One compound showed good inhibition (IC50 1.1 μM) and >10 fold selectivity towards PDE4B over D that was supported by docking studies. This compound also showed significant inhibition of TNF-α and no major toxicities in cell lines and a zebrafish embryo model except the teratogenic effects to be re-assessed in rodents.
Medicinal Chemistry Research, 2013
ABSTRACT Indian traditional medicinal plant Piper attenuatum (Buch-Ham) was investigated for its ... more ABSTRACT Indian traditional medicinal plant Piper attenuatum (Buch-Ham) was investigated for its antioxidant and anticancer activity. Three extracts were prepared using ethyl acetate, ethanol and methanol. In vitro antioxidant activity was performed by ABTS {2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)} free radical scavenging method. All three extracts reduced the free radicals produced by ABTS in a concentration dependent manner which could be compared to the standard (Gallic acid). Invitro anticancer activity of all extracts was carried out by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay method against MCF7 (Michigan Cancer Foundation-7) cell lines. None of the extract showed anticancer activity when compared with the standard (Mitomycin-C) indicating that p. attenuatum is deprived of antiproliferative or cytotoxic components.
Medicinal Chemistry Research, 2013
Abstract The present study describes identification of a novel lead molecule ZINC02765569 for inh... more Abstract The present study describes identification of a novel lead molecule ZINC02765569 for inhibition of protein tyrosine phosphatase 1B (PTP1B) enzyme by a high-throughput virtual screening of Zinc database against catalytic domain of PTP1B employing docking ...
Medicinal Chemistry Research, 2012
ABSTRACT A QSAR study has been performed on a series of aminopyrazolopyridine urea derivatives wi... more ABSTRACT A QSAR study has been performed on a series of aminopyrazolopyridine urea derivatives with potent VEGFR kinase inhibitory activity. Structural features responsible for the activity of the compounds were characterized by using physicochemical, topological, and electrotopological descriptors, calculated from the Molecular Design Suite software (V-life MDSTM 3.5). Correlations between the inhibitory activities (KDR and KDRcell) of aminopyrazolopyridine urea derivatives and the calculated descriptors were established through simulated annealing method. The best QSAR models generated from the study explain 89 and 88% of the variation in KDR and KDRcell inhibitory activities, respectively. Internal and external validation methods were used to evaluate the predictive capacity of the generated models. The significant cross-validated correlation coefficient (Q2[0.6) and other statistical parameters suggest that the models exhibited considerable predictivity. The generated QSAR models divulge that factors related to lipophilicity and topological state of atoms in the molecule influences KDR and KDRcell inhibitory activities of aminopyrazolopyridine urea derivatives.
Medicinal Chemistry Research, 2013
ABSTRACT This article describes design, synthesis, and molecular modeling studies of the ZINC0276... more ABSTRACT This article describes design, synthesis, and molecular modeling studies of the ZINC02765569 derivatives as potent protein tyrosine phosphatase 1B (PTP1B) inhibitors, which was previously reported as a vHTS hit (ZINC02765569) by our laboratory. Ten compounds were synthesized and characterized by IR, MASS, and NMR followed by in vitro screening for PTP1B inhibition and glucose uptake in skeletal muscle L6 myotubes. The most potent compound 3j shows 66.4 % in vitro PTP1B inhibition and 39.6 % increase in glucose uptake. Glide was used to study the nature of interactions governing binding of designed molecules with active site of the PTP1B enzyme.
Letters in Drug Design Amp Discovery, 2011
Medicinal Chemistry Research
Letters in Drug Design & Discovery, 2011
... Moorthy 1,4 , Hoyun Lee 2,3 , Kapendra Sahu 1 , Girdhar Singh Deora 1 and Piyush Trivedi* ,1 ... more ... Moorthy 1,4 , Hoyun Lee 2,3 , Kapendra Sahu 1 , Girdhar Singh Deora 1 and Piyush Trivedi* ,1 1School of Pharmaceutical Sciences, Rajiv Gandhi Technical University, Airport Bypass Road, Gandhi Nagar, Bhopal-462036 (MP), India 2Tumour Biology Group, Northeastern ...
Tetrahedron Letters, 2013
European Journal of Medicinal Chemistry, 2014
The link between PDE4 and apoptosis prompted us to design and synthesize for the first time a ser... more The link between PDE4 and apoptosis prompted us to design and synthesize for the first time a series of novel 1-thienyl pyrroloquinoxalines as potential PDE4 inhibitors/apoptotic agents. A ligand-free Pd-catalyzed C-N cross-coupling/cyclization strategy has been developed for the rapid and milder access to this class of compounds some of which showed interesting pharmacological properties when tested in vitro and in zebrafish embryos.
Tetrahedron Letters, 2014
ABSTRACT The linkage between dopamine D2 receptors and PDE activity via cAMP prompted us to desig... more ABSTRACT The linkage between dopamine D2 receptors and PDE activity via cAMP prompted us to design a series of novel N-(3-arylprop-2-ynyl)substituted olanzapine derivatives as potential inhibitors of PDE4B. The target compounds were conveniently prepared by using a simple and inexpensive method involving Pd/C-mediated C-C bond forming reaction under Sonogashira conditions. A number of compounds were synthesized by using this strategy in good yields. Some of the compounds showed promising inhibition of PDE4B when tested in vitro that was supported by the docking studies.
Tetrahedron Letters, 2012
ABSTRACT AgNO3 facilitated the intramolecular ring closure of o-(1-alkynyl)benzenesulfonamides vi... more ABSTRACT AgNO3 facilitated the intramolecular ring closure of o-(1-alkynyl)benzenesulfonamides via a regioselective C-N bond forming reaction leading to the formation of 3-substituted benzothiazine derivatives. A number of compounds were prepared in good yields by using this inexpensive and safe methodology. All the compounds synthesized were evaluated for their cyclooxygenase (COX) inhibiting properties in vitro. A number of compounds that do not contain an enolic hydroxyl group showed selectivities toward COX-2 over COX-1 inhibition. This was further supported by the predictive binding mode of two compounds with COX-1 and -2 proteins through molecular docking studies.
Synthetic Communications, 2014
ABSTRACT A simple and inexpensive synthesis of novel 2-(3-oxo-3-arylpropyl)-2,3-dihydro-1H-inden-... more ABSTRACT A simple and inexpensive synthesis of novel 2-(3-oxo-3-arylpropyl)-2,3-dihydro-1H-inden-1-one derivatives has been achieved via Pd/C-mediated arylation followed by I2-mediated regioselectivehydration of 2-(prop-2-ynyl)-2,3-dihydro-1H-inden-1-ones. A wide variety of 3-aryl substituted 2-propynyl indanone derivatives were conveniently prepared by using 10% Pd/C-PPh3-CuI as a catalyst system some of which were used to prepare the corresponding ketones via alkyne hydration in the presence of catalytic I2. In an in vitro study a representative compound showed inhibition of PDE4B (phosphodiesterase type 4B) and binding with this protein in silico.
Organic & Biomolecular Chemistry, 2013
A series of 1,3-disubstituted pyrrolo[2,3-b]quinoxalines has been designed for the potential inhi... more A series of 1,3-disubstituted pyrrolo[2,3-b]quinoxalines has been designed for the potential inhibition of PDE4 without inhibiting luciferase. A ligand/PTC (phase transfer catalyst) free intramolecular Heck cyclization strategy was used to prepare these compounds, some of which showed significant inhibition of PDE4B (IC50≈ 5-14 μM) and growth inhibition of oral cancer cells (CAL 27) but not inhibition of luciferase in vitro. They also showed acceptable safety profiles but no apoptosis in zebrafish embryos.
Organic & Biomolecular Chemistry, 2013
A series of functionalized phenyl oxazole derivatives was designed, synthesized and screened in v... more A series of functionalized phenyl oxazole derivatives was designed, synthesized and screened in vitro for their activities against LSD1 and for effects on viability of cervical and breast cancer cells, and in vivo for effects using zebrafish embryos. These compounds are likely to act via multiple epigenetic mechanisms specific to cancer cells including LSD1 inhibition.
Organic & Biomolecular Chemistry, 2013
A new strategy for converting antipsychotic drug olanzapine into PDE4 inhibitors is described via... more A new strategy for converting antipsychotic drug olanzapine into PDE4 inhibitors is described via the design and Pd/C mediated synthesis of novel N-indolylmethyl olanzapine derivatives. One compound showed good inhibition (IC50 1.1 μM) and >10 fold selectivity towards PDE4B over D that was supported by docking studies. This compound also showed significant inhibition of TNF-α and no major toxicities in cell lines and a zebrafish embryo model except the teratogenic effects to be re-assessed in rodents.
Medicinal Chemistry Research, 2013
ABSTRACT Indian traditional medicinal plant Piper attenuatum (Buch-Ham) was investigated for its ... more ABSTRACT Indian traditional medicinal plant Piper attenuatum (Buch-Ham) was investigated for its antioxidant and anticancer activity. Three extracts were prepared using ethyl acetate, ethanol and methanol. In vitro antioxidant activity was performed by ABTS {2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)} free radical scavenging method. All three extracts reduced the free radicals produced by ABTS in a concentration dependent manner which could be compared to the standard (Gallic acid). Invitro anticancer activity of all extracts was carried out by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay method against MCF7 (Michigan Cancer Foundation-7) cell lines. None of the extract showed anticancer activity when compared with the standard (Mitomycin-C) indicating that p. attenuatum is deprived of antiproliferative or cytotoxic components.
Medicinal Chemistry Research, 2013
Abstract The present study describes identification of a novel lead molecule ZINC02765569 for inh... more Abstract The present study describes identification of a novel lead molecule ZINC02765569 for inhibition of protein tyrosine phosphatase 1B (PTP1B) enzyme by a high-throughput virtual screening of Zinc database against catalytic domain of PTP1B employing docking ...
Medicinal Chemistry Research, 2012
ABSTRACT A QSAR study has been performed on a series of aminopyrazolopyridine urea derivatives wi... more ABSTRACT A QSAR study has been performed on a series of aminopyrazolopyridine urea derivatives with potent VEGFR kinase inhibitory activity. Structural features responsible for the activity of the compounds were characterized by using physicochemical, topological, and electrotopological descriptors, calculated from the Molecular Design Suite software (V-life MDSTM 3.5). Correlations between the inhibitory activities (KDR and KDRcell) of aminopyrazolopyridine urea derivatives and the calculated descriptors were established through simulated annealing method. The best QSAR models generated from the study explain 89 and 88% of the variation in KDR and KDRcell inhibitory activities, respectively. Internal and external validation methods were used to evaluate the predictive capacity of the generated models. The significant cross-validated correlation coefficient (Q2[0.6) and other statistical parameters suggest that the models exhibited considerable predictivity. The generated QSAR models divulge that factors related to lipophilicity and topological state of atoms in the molecule influences KDR and KDRcell inhibitory activities of aminopyrazolopyridine urea derivatives.
Medicinal Chemistry Research, 2013
ABSTRACT This article describes design, synthesis, and molecular modeling studies of the ZINC0276... more ABSTRACT This article describes design, synthesis, and molecular modeling studies of the ZINC02765569 derivatives as potent protein tyrosine phosphatase 1B (PTP1B) inhibitors, which was previously reported as a vHTS hit (ZINC02765569) by our laboratory. Ten compounds were synthesized and characterized by IR, MASS, and NMR followed by in vitro screening for PTP1B inhibition and glucose uptake in skeletal muscle L6 myotubes. The most potent compound 3j shows 66.4 % in vitro PTP1B inhibition and 39.6 % increase in glucose uptake. Glide was used to study the nature of interactions governing binding of designed molecules with active site of the PTP1B enzyme.