Dr. Achintya Saha | University of Calcutta (original) (raw)
Papers by Dr. Achintya Saha
PLOS ONE
Dengue virus (DENV) encodes a unique protease (NS3/NS2B) essential for its maturation and infecti... more Dengue virus (DENV) encodes a unique protease (NS3/NS2B) essential for its maturation and infectivity and, it has become a key target for anti-viral drug design to treat dengue and other flavivirus related infections. Present investigation established that some of the drug molecules currently used mainly in cancer treatment are susceptible to bind non-active site (allosteric site/ cavity) of the NS3 protease enzyme of dengue virus. Computational screening and molecular docking analysis found that dabrafenib, idelalisib and nintedanib can bind at the allosteric site of the enzyme. The binding of the molecules to the allosteric site found to be stabilized via pi-cation and hydrophobic interactions, hydrogen-bond formation and π-stacking interaction with the molecules. Several interacting residues of the enzyme were common in all the five serotypes. However, the interaction/stabilizing forces were not uniformly distributed; the π-stacking was dominated with DENV3 proteases, whereas, a ...
Molecular Diversity
In this study, a set of dietary polyphenols was comprehensively studied for the selective identif... more In this study, a set of dietary polyphenols was comprehensively studied for the selective identification of the potential inhibitors/modulators for galectin-1. Galectin-1 is a potent prognostic indicator of tumor progression and a highly regarded therapeutic target for various pathological conditions. This indicator is composed of a highly conserved carbohydrate recognition domain (CRD) that accounts for the binding affinity of β-galactosides. Although some small molecules have been identified as galectin-1 inhibitors/modulators, there are limited studies on the identification of novel compounds against this attractive therapeutic target. The extensive computational techniques include potential drug binding site recognition on galectin-1, binding affinity predictions of ~ 500 polyphenols, molecular docking, and dynamic simulations of galectin-1 with selective dietary polyphenol modulators, followed by the estimation of binding free energy for the identification of dietary polyphenol...
Molecular Diversity
Worldwide coronavirus disease 2019 (COVID-19) outbreak is still threatening global health since i... more Worldwide coronavirus disease 2019 (COVID-19) outbreak is still threatening global health since its outbreak first reported in the late 2019. The causative novel virus has been designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although COVID-19 emergent with significant mortality, there is no availability of definite treatment measures. It is now extremely desirable to identify potential chemical entities against SARS-CoV-2 for the treatment of COVID-19. In the present study, a state-of-art virtual screening protocol was implemented on three anti-viral specific chemical libraries against SARS-CoV-2 main protease (Mpro). Particularly, viewing the large-scale biological role of Mpro in the viral replication process it has been considered as a prospective anti-viral drug target. Herein, on collected 79,892 compounds, hierarchical multistep docking followed by relative binding free energy estimation has been performed. Thereafter, implying a user-defined XP-doc...
Molecules
The present study evaluated the therapeutic potential of myricitrin (Myr), a glycosyloxyflavone e... more The present study evaluated the therapeutic potential of myricitrin (Myr), a glycosyloxyflavone extracted from Myrica esculenta bark, against diabetic nephropathy. Myr exhibited a significant hypoglycemic effect in high fat-fed and a single low-dose streptozotocin-induced type 2 diabetic (T2D) rats. Myr was found to improve glucose uptake by the skeletal muscle via activating IRS-1/PI3K/Akt/GLUT4 signaling in vitro and in vivo. Myr significantly attenuated high glucose (HG)-induced toxicity in NRK cells and in the kidneys of T2D rats. In this study, hyperglycemia caused nephrotoxicity via endorsing oxidative stress and inflammation resulting in the induction of apoptosis, fibrosis, and inflammatory damages. Myr was found to attenuate oxidative stress via scavenging/neutralizing oxidative radicals and improving endogenous redox defense through Nrf-2 activation in both in vitro and in vivo systems. Myr was also found to attenuate diabetes-triggered renal inflammation via suppressing N...
Journal of Biomolecular Structure and Dynamics
Journal of Chromatographic Science
Nateglinide (NAT) and Pioglitazone (PIO) are an antidiabetic drugs combination and currently unde... more Nateglinide (NAT) and Pioglitazone (PIO) are an antidiabetic drugs combination and currently under clinical trial in countries like Japan. In this study, an alternative, a simple, sensitive high-performance liquid chromatography method has been developed (limit of detection: 15 ng/mL and limit of quantification: 50 ng/mL) for simultaneous estimation of this drug combination in rat plasma. Most remarkably, bioavailability of NAT has been increased markedly on coadministration with PIO, than when it was administered alone. Thus, PIO is assumed to retard the catabolism of NAT by inhibiting metabolic liver-microsomal enzyme, especially CYP2C9. Using a Waters Nova-Pak C 18 column (150 × 3.9 mm, 4 μm) and a mobile phase of acetonitrile: 10 mM KH2PO4 (60: 40, V/V (volume by volume)) pH 3.5, the analysis was performed at 210 nm with a flow rate of 1.5 mL/min. In silico docking via molecular dynamics simulation revealed that NAT-CYP2C9 binding affinity may be reduced after PIO attachment, pr...
International Journal of Molecular Sciences
The present investigation was executed to reveal the protective mechanism of rosmarinic acid (RA)... more The present investigation was executed to reveal the protective mechanism of rosmarinic acid (RA) against cadmium (Cd)-induced nephrotoxicity. RA exhibited a concentration-dependent anti-apoptotic effect against CdCl2 in isolated mouse proximal tubular epithelial cells. Cd treatment significantly (p < 0.01) imparted oxidative stress to the renal cells via excessive ROS production, triggering NO level, NADPH oxidase activation, and impairment of cellular redox defense system. Cd-mediated oxidative stress significantly (p < 0.01) endorsed apoptosis to the murine kidney cells by triggering NF-κB/PKC-δ/TNFR2 activation. In addition, CdCl2 induced renal fibrosis by triggering TGF-β1/SMAD3/α-SMA/collagen signaling within renal cells. On the other hand, RA significantly (p < 0.05–0.01) attenuated Cd-provoked oxidative stress and associated pathological signal transduction in murine renal cells. RA treatment also could significantly (p < 0.05–0.01) reciprocate Cd-mediated pathol...
Molecules
Cadmium (Cd) imparts nephrotoxicity via triggering oxidative stress and pathological signal trans... more Cadmium (Cd) imparts nephrotoxicity via triggering oxidative stress and pathological signal transductions in renal cells. The present study was performed to explore the protective mechanism of carnosic acid (CA), a naturally occurring antioxidant compound, against cadmium chloride (CdCl2)-provoked nephrotoxicity employing suitable in vitro and in vivo assays. CA (5 µM) exhibited an anti-apoptotic effect against CdCl2 (40 µM) in normal kidney epithelial (NKE) cells evidenced from cell viability, image, and flow cytometry assays. In this study, CdCl2 treatment enhanced oxidative stress by triggering free radical production, suppressing the endogenous redox defence system, and inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2) activation in NKE cells and mouse kidneys. Moreover, CdCl2 treatment significantly endorsed apoptosis and fibrosis via activation of apoptotic and transforming growth factor (TGF)-β1/mothers against decapentaplegic homolog (Smad)/collagen IV signalling...
International Journal of Quantitative Structure-Property Relationships
Pharmacoinformatics strategies have been applied to explore promising selective estrogen receptor... more Pharmacoinformatics strategies have been applied to explore promising selective estrogen receptor (ER) modulators (SERMs). A set of non-steroidal ligands was considered for both ERα and ERβ subtypes. Best pharmacophore models revealed with importance of hydrogen bond acceptor and hydrophobicity for both subtypes, along with an aromatic ring and hydrogen bond donor for α and β subtypes, respectively. Both models were validated, and further considered for virtual screening of National Cancer Institute database. Initial hits were sorted with a number of criteria, and finally the molecules have been proposed as promising SERMs. A molecular docking study explained that screened ligands formed a number of binding interactions with both ERs. The subtype receptors in complex with active and screened compounds were considered for molecular simulations to compare stability of the complexes. An analysis of binding energy found that screened ligands hold a strong affinity towards the selective ...
Computational biology and chemistry, 2018
Tyrosinase is a metal containing multifunctional enzymes found in animals, fruits and vegetables ... more Tyrosinase is a metal containing multifunctional enzymes found in animals, fruits and vegetables and constitutes the primary cause for diseases resulting from overproduction of melanin as well as for browning of fruits. Inhibitors of the enzyme have thus gained increased importance in food and cosmetic industry. In the present work, a group of azole derivatives with tyrosinase inhibitory activity were explored to analyse the prime structural attributes of the potent inhibitors. In silico models have been developed in order to have a close insight regarding features of the molecular fragments that may affect the activity of the molecules conducively. The biological pharmacophore of the inhibitors that accounts for their interaction with the tyrosinase enzyme has been ascertained based on the development of a 3D pharmacophore model. The models thus developed were subsequently utilised for screening a set of compounds that were previously synthesised in-house and were reported to posse...
Oxidative medicine and cellular longevity, 2018
The present studies have been executed to explore the protective mechanism of carnosic acid (CA) ... more The present studies have been executed to explore the protective mechanism of carnosic acid (CA) against NaAsO-induced hepatic injury. CA exhibited a concentration dependent (1-4 M) increase in cell viability against NaAsO (12 M) in murine hepatocytes. NaAsO treatment significantly enhanced the ROS-mediated oxidative stress in the hepatic cells both in and systems. Significant activation of MAPK, NF-B, p53, and intrinsic and extrinsic apoptotic signaling was observed in NaAsO-exposed hepatic cells. CA could significantly counteract with redox stress and ROS-mediated signaling and thereby attenuated NaAsO-mediated hepatotoxicity. NaAsO (10 mg/kg) treatment caused significant increment in the As bioaccumulation, cytosolic ATP level, DNA fragmentation, and oxidation in the liver of experimental mice ( = 6). The serum biochemical and haematological parameters were significantly altered in the NaAsO-exposed mice ( = 6). Simultaneous treatment with CA (10 and 20 mg/kg) could significantly...
Drug research, 2018
We have evaluated the LDH inhibitory property of novel pyrazolo[4',3':5,6][1,4]oxathiino[... more We have evaluated the LDH inhibitory property of novel pyrazolo[4',3':5,6][1,4]oxathiino[2,3-b]pyrazine derivatives which have been synthesized from easily available starting materials through a one-pot protocol that offers the use of elemental sulfur as the sulfur source. These newly synthesized compounds may aid to drug development for neoplastic and non-neoplastic diseases characterized by increased glucose metabolism. Additionally, they may act as suitable starting materials which can be further structurally modified for the development of new LDH inhibitors with higher efficacy and specificity.
Nanomedicine: Nanotechnology, Biology and Medicine
Elevated serum interleukins (IL-6, IL-1β) over baseline concentration help in blastocyst adhesion... more Elevated serum interleukins (IL-6, IL-1β) over baseline concentration help in blastocyst adhesion to the uterine endometrium in the early phase of pregnancy. A nano PLA (Piperolactam A)-HPBCD (2-hydroxy-propyl-β-cyclodextrin) inclusion complex was developed as an interleukin down-regulator that exhibited 100% anti-implantation activity in rodents at a dose as low as 2.5-5.0 mg/kg. On metabolomics study, among major glyco-lipo-protein metabolites, only serum low-density lipoprotein (LDL) or very low-density lipoprotein (VLDL) levels revealed alteration by the formulation. Administration of PLA-HPBCD did not cause changes in serum estrogen and progesterone levels. However, IL-6 and IL-1β failed to increase post PLA-HPBCD administration; hence, it is assumed to be the mode of the drug's abortifacient action. In addition, absence of signs of either acute or chronic toxicity suggests the formulation was considerably non-toxic. Therefore, the nano-PLA conjugate promises as a non-steroidal contraceptive lead apart from ormeloxifene, the only non-steroidal anti-fertility agent currently available globally.
Frontiers in Pharmacology
Bhattacharjee et al. Protocatechuic Acid Suppresses Diabetic Cardiomyopathy different signaling m... more Bhattacharjee et al. Protocatechuic Acid Suppresses Diabetic Cardiomyopathy different signaling molecules, PI3K, IRS, Akt, AMPK PKC, NF-κB and PARP, involved in glucose utilization and inflammatory pathophysiology. In silico ADME study predicted that protocatechuic acid would support the drug-likeness character. Combining all, results would suggest a possibility of protocatechuic acid to be a new therapeutic agent for DC in future.
Scientific reports, Jan 14, 2018
Eye irritation assessment is compulsory to anticipate health risks in military personnel exposed ... more Eye irritation assessment is compulsory to anticipate health risks in military personnel exposed to riot control agents such as capsaicin, the principal constituent of oleoresin capsicum, or pepper sprays. The present work investigates certain fundamental yet unaddressed pharmacological manifestations on ocular exposure to capsaicin. Ocular pharmacology of capsaicin was studied using acute eye irritation (AEI), bovine corneal opacity and permeability (BCOP) assay, corneal fluorescein staining and indirect ophthalmoscopy studies, transcorneal permeation, Schirmer tear secretion test, nerve conduction velocity study and enzyme-linked immunosorbent assay (ELISA). Additionally, histopathology and scanning electron microscopy (SEM) of bovine corneas and rat optic nerves were done to further estimate capsaicin induced morphological variations. Our findings demonstrated that AEI, BCOP, corneal fluorescein staining and indirect ophthalmoscopy were useful in assessing capsaicin induced ocula...
ACS omega, Jan 28, 2018
Engaging Raman spectroscopy as a primary tool, we investigated the early events of insulin fibril... more Engaging Raman spectroscopy as a primary tool, we investigated the early events of insulin fibrilization and determined the structural content present in oligomer and protofibrils that are formed as intermediates in the fibril formation pathway. Insulin oligomer, as obtained upon incubation of zinc-free insulin at 60 °C, was mostly spherical in shape, with a diameter of 3-5 nm. Longer incubation produced "necklace"-like beaded protofibrillar assembly species. These intermediates eventually transformed into 5-8 nm thick fibers with smooth surface texture. A broad amide I band in the Raman spectrum of insulin monomer appeared at 1659 cm, with a shoulder band at 1676 cm. This signature suggested the presence of major helical and extended secondary structure of the protein backbone. In the oligomeric state, the protein maintained its helical imprint (∼50%) and no substantial increment of the compact cross-β-sheet structure was observed. A nonamide helix signature band at 940 c...
European journal of pharmacology, Jan 15, 2018
Capsaicin is the principal constituent of oleoresin capsicum, or pepper spray, as it is commonly ... more Capsaicin is the principal constituent of oleoresin capsicum, or pepper spray, as it is commonly known. Pepper sprays are frequently used in riot control situations by defence organizations all over the world to deal with uncontrolled civil or criminal disturbances. Although capsaicin is noted for its irritant and inflammatory properties, the ocular profile of capsaicin has not been specifically studied and interpreted. The present review analyses the mammalian opthalmological profile of capsaicin and its pharmacological and toxicological manifestations including capsaicin induced corneal changes, neurogenic inflammation, neuroprotective influences on retinal ganglion cells (RGCs), depletion of neuropeptide content in sensory nerve terminals etc. Substantial views on the capsaicin receptor Transient Receptor Potential Vanilloid V1 (TRPV1), its presence, significance and capsaicin induced mediations have been presented. Studies conducted previously on the reversal of capsaicin evoked...
International Journal of Quantitative Structure-Property Relationships
The present approach has aimed to investigate the physicochemical and structural requirements of ... more The present approach has aimed to investigate the physicochemical and structural requirements of a molecule to impart potential and selective PPARa agonistic activity using various ligand-based and structure-based molecular modeling techniques. These studies suggest the presence oxo heterocyclic ring connected with lipophilic substituents (phenyl, flurophenyl or any hydropbic alkyl chain) may responsible for hydrophobic interaction with the receptor. Both regression-based and classification-based QSAR, and HQSAR models infer that the ether linkage is very crucial for the activity, where as long alkyl chain or acyclic ring and the chloride substituent have detrimental effects. The pharmacophore models strongly depict the presence of two acceptors and hydrophobic region are very much essential for promising activity. The docking and MD studies suggest the presence of carboxyl group is essential for H-bond interaction with catalytic residues. The cheminformatics study provides key info...
Medicinal Chemistry Research
PLOS ONE
Dengue virus (DENV) encodes a unique protease (NS3/NS2B) essential for its maturation and infecti... more Dengue virus (DENV) encodes a unique protease (NS3/NS2B) essential for its maturation and infectivity and, it has become a key target for anti-viral drug design to treat dengue and other flavivirus related infections. Present investigation established that some of the drug molecules currently used mainly in cancer treatment are susceptible to bind non-active site (allosteric site/ cavity) of the NS3 protease enzyme of dengue virus. Computational screening and molecular docking analysis found that dabrafenib, idelalisib and nintedanib can bind at the allosteric site of the enzyme. The binding of the molecules to the allosteric site found to be stabilized via pi-cation and hydrophobic interactions, hydrogen-bond formation and π-stacking interaction with the molecules. Several interacting residues of the enzyme were common in all the five serotypes. However, the interaction/stabilizing forces were not uniformly distributed; the π-stacking was dominated with DENV3 proteases, whereas, a ...
Molecular Diversity
In this study, a set of dietary polyphenols was comprehensively studied for the selective identif... more In this study, a set of dietary polyphenols was comprehensively studied for the selective identification of the potential inhibitors/modulators for galectin-1. Galectin-1 is a potent prognostic indicator of tumor progression and a highly regarded therapeutic target for various pathological conditions. This indicator is composed of a highly conserved carbohydrate recognition domain (CRD) that accounts for the binding affinity of β-galactosides. Although some small molecules have been identified as galectin-1 inhibitors/modulators, there are limited studies on the identification of novel compounds against this attractive therapeutic target. The extensive computational techniques include potential drug binding site recognition on galectin-1, binding affinity predictions of ~ 500 polyphenols, molecular docking, and dynamic simulations of galectin-1 with selective dietary polyphenol modulators, followed by the estimation of binding free energy for the identification of dietary polyphenol...
Molecular Diversity
Worldwide coronavirus disease 2019 (COVID-19) outbreak is still threatening global health since i... more Worldwide coronavirus disease 2019 (COVID-19) outbreak is still threatening global health since its outbreak first reported in the late 2019. The causative novel virus has been designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although COVID-19 emergent with significant mortality, there is no availability of definite treatment measures. It is now extremely desirable to identify potential chemical entities against SARS-CoV-2 for the treatment of COVID-19. In the present study, a state-of-art virtual screening protocol was implemented on three anti-viral specific chemical libraries against SARS-CoV-2 main protease (Mpro). Particularly, viewing the large-scale biological role of Mpro in the viral replication process it has been considered as a prospective anti-viral drug target. Herein, on collected 79,892 compounds, hierarchical multistep docking followed by relative binding free energy estimation has been performed. Thereafter, implying a user-defined XP-doc...
Molecules
The present study evaluated the therapeutic potential of myricitrin (Myr), a glycosyloxyflavone e... more The present study evaluated the therapeutic potential of myricitrin (Myr), a glycosyloxyflavone extracted from Myrica esculenta bark, against diabetic nephropathy. Myr exhibited a significant hypoglycemic effect in high fat-fed and a single low-dose streptozotocin-induced type 2 diabetic (T2D) rats. Myr was found to improve glucose uptake by the skeletal muscle via activating IRS-1/PI3K/Akt/GLUT4 signaling in vitro and in vivo. Myr significantly attenuated high glucose (HG)-induced toxicity in NRK cells and in the kidneys of T2D rats. In this study, hyperglycemia caused nephrotoxicity via endorsing oxidative stress and inflammation resulting in the induction of apoptosis, fibrosis, and inflammatory damages. Myr was found to attenuate oxidative stress via scavenging/neutralizing oxidative radicals and improving endogenous redox defense through Nrf-2 activation in both in vitro and in vivo systems. Myr was also found to attenuate diabetes-triggered renal inflammation via suppressing N...
Journal of Biomolecular Structure and Dynamics
Journal of Chromatographic Science
Nateglinide (NAT) and Pioglitazone (PIO) are an antidiabetic drugs combination and currently unde... more Nateglinide (NAT) and Pioglitazone (PIO) are an antidiabetic drugs combination and currently under clinical trial in countries like Japan. In this study, an alternative, a simple, sensitive high-performance liquid chromatography method has been developed (limit of detection: 15 ng/mL and limit of quantification: 50 ng/mL) for simultaneous estimation of this drug combination in rat plasma. Most remarkably, bioavailability of NAT has been increased markedly on coadministration with PIO, than when it was administered alone. Thus, PIO is assumed to retard the catabolism of NAT by inhibiting metabolic liver-microsomal enzyme, especially CYP2C9. Using a Waters Nova-Pak C 18 column (150 × 3.9 mm, 4 μm) and a mobile phase of acetonitrile: 10 mM KH2PO4 (60: 40, V/V (volume by volume)) pH 3.5, the analysis was performed at 210 nm with a flow rate of 1.5 mL/min. In silico docking via molecular dynamics simulation revealed that NAT-CYP2C9 binding affinity may be reduced after PIO attachment, pr...
International Journal of Molecular Sciences
The present investigation was executed to reveal the protective mechanism of rosmarinic acid (RA)... more The present investigation was executed to reveal the protective mechanism of rosmarinic acid (RA) against cadmium (Cd)-induced nephrotoxicity. RA exhibited a concentration-dependent anti-apoptotic effect against CdCl2 in isolated mouse proximal tubular epithelial cells. Cd treatment significantly (p < 0.01) imparted oxidative stress to the renal cells via excessive ROS production, triggering NO level, NADPH oxidase activation, and impairment of cellular redox defense system. Cd-mediated oxidative stress significantly (p < 0.01) endorsed apoptosis to the murine kidney cells by triggering NF-κB/PKC-δ/TNFR2 activation. In addition, CdCl2 induced renal fibrosis by triggering TGF-β1/SMAD3/α-SMA/collagen signaling within renal cells. On the other hand, RA significantly (p < 0.05–0.01) attenuated Cd-provoked oxidative stress and associated pathological signal transduction in murine renal cells. RA treatment also could significantly (p < 0.05–0.01) reciprocate Cd-mediated pathol...
Molecules
Cadmium (Cd) imparts nephrotoxicity via triggering oxidative stress and pathological signal trans... more Cadmium (Cd) imparts nephrotoxicity via triggering oxidative stress and pathological signal transductions in renal cells. The present study was performed to explore the protective mechanism of carnosic acid (CA), a naturally occurring antioxidant compound, against cadmium chloride (CdCl2)-provoked nephrotoxicity employing suitable in vitro and in vivo assays. CA (5 µM) exhibited an anti-apoptotic effect against CdCl2 (40 µM) in normal kidney epithelial (NKE) cells evidenced from cell viability, image, and flow cytometry assays. In this study, CdCl2 treatment enhanced oxidative stress by triggering free radical production, suppressing the endogenous redox defence system, and inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2) activation in NKE cells and mouse kidneys. Moreover, CdCl2 treatment significantly endorsed apoptosis and fibrosis via activation of apoptotic and transforming growth factor (TGF)-β1/mothers against decapentaplegic homolog (Smad)/collagen IV signalling...
International Journal of Quantitative Structure-Property Relationships
Pharmacoinformatics strategies have been applied to explore promising selective estrogen receptor... more Pharmacoinformatics strategies have been applied to explore promising selective estrogen receptor (ER) modulators (SERMs). A set of non-steroidal ligands was considered for both ERα and ERβ subtypes. Best pharmacophore models revealed with importance of hydrogen bond acceptor and hydrophobicity for both subtypes, along with an aromatic ring and hydrogen bond donor for α and β subtypes, respectively. Both models were validated, and further considered for virtual screening of National Cancer Institute database. Initial hits were sorted with a number of criteria, and finally the molecules have been proposed as promising SERMs. A molecular docking study explained that screened ligands formed a number of binding interactions with both ERs. The subtype receptors in complex with active and screened compounds were considered for molecular simulations to compare stability of the complexes. An analysis of binding energy found that screened ligands hold a strong affinity towards the selective ...
Computational biology and chemistry, 2018
Tyrosinase is a metal containing multifunctional enzymes found in animals, fruits and vegetables ... more Tyrosinase is a metal containing multifunctional enzymes found in animals, fruits and vegetables and constitutes the primary cause for diseases resulting from overproduction of melanin as well as for browning of fruits. Inhibitors of the enzyme have thus gained increased importance in food and cosmetic industry. In the present work, a group of azole derivatives with tyrosinase inhibitory activity were explored to analyse the prime structural attributes of the potent inhibitors. In silico models have been developed in order to have a close insight regarding features of the molecular fragments that may affect the activity of the molecules conducively. The biological pharmacophore of the inhibitors that accounts for their interaction with the tyrosinase enzyme has been ascertained based on the development of a 3D pharmacophore model. The models thus developed were subsequently utilised for screening a set of compounds that were previously synthesised in-house and were reported to posse...
Oxidative medicine and cellular longevity, 2018
The present studies have been executed to explore the protective mechanism of carnosic acid (CA) ... more The present studies have been executed to explore the protective mechanism of carnosic acid (CA) against NaAsO-induced hepatic injury. CA exhibited a concentration dependent (1-4 M) increase in cell viability against NaAsO (12 M) in murine hepatocytes. NaAsO treatment significantly enhanced the ROS-mediated oxidative stress in the hepatic cells both in and systems. Significant activation of MAPK, NF-B, p53, and intrinsic and extrinsic apoptotic signaling was observed in NaAsO-exposed hepatic cells. CA could significantly counteract with redox stress and ROS-mediated signaling and thereby attenuated NaAsO-mediated hepatotoxicity. NaAsO (10 mg/kg) treatment caused significant increment in the As bioaccumulation, cytosolic ATP level, DNA fragmentation, and oxidation in the liver of experimental mice ( = 6). The serum biochemical and haematological parameters were significantly altered in the NaAsO-exposed mice ( = 6). Simultaneous treatment with CA (10 and 20 mg/kg) could significantly...
Drug research, 2018
We have evaluated the LDH inhibitory property of novel pyrazolo[4',3':5,6][1,4]oxathiino[... more We have evaluated the LDH inhibitory property of novel pyrazolo[4',3':5,6][1,4]oxathiino[2,3-b]pyrazine derivatives which have been synthesized from easily available starting materials through a one-pot protocol that offers the use of elemental sulfur as the sulfur source. These newly synthesized compounds may aid to drug development for neoplastic and non-neoplastic diseases characterized by increased glucose metabolism. Additionally, they may act as suitable starting materials which can be further structurally modified for the development of new LDH inhibitors with higher efficacy and specificity.
Nanomedicine: Nanotechnology, Biology and Medicine
Elevated serum interleukins (IL-6, IL-1β) over baseline concentration help in blastocyst adhesion... more Elevated serum interleukins (IL-6, IL-1β) over baseline concentration help in blastocyst adhesion to the uterine endometrium in the early phase of pregnancy. A nano PLA (Piperolactam A)-HPBCD (2-hydroxy-propyl-β-cyclodextrin) inclusion complex was developed as an interleukin down-regulator that exhibited 100% anti-implantation activity in rodents at a dose as low as 2.5-5.0 mg/kg. On metabolomics study, among major glyco-lipo-protein metabolites, only serum low-density lipoprotein (LDL) or very low-density lipoprotein (VLDL) levels revealed alteration by the formulation. Administration of PLA-HPBCD did not cause changes in serum estrogen and progesterone levels. However, IL-6 and IL-1β failed to increase post PLA-HPBCD administration; hence, it is assumed to be the mode of the drug's abortifacient action. In addition, absence of signs of either acute or chronic toxicity suggests the formulation was considerably non-toxic. Therefore, the nano-PLA conjugate promises as a non-steroidal contraceptive lead apart from ormeloxifene, the only non-steroidal anti-fertility agent currently available globally.
Frontiers in Pharmacology
Bhattacharjee et al. Protocatechuic Acid Suppresses Diabetic Cardiomyopathy different signaling m... more Bhattacharjee et al. Protocatechuic Acid Suppresses Diabetic Cardiomyopathy different signaling molecules, PI3K, IRS, Akt, AMPK PKC, NF-κB and PARP, involved in glucose utilization and inflammatory pathophysiology. In silico ADME study predicted that protocatechuic acid would support the drug-likeness character. Combining all, results would suggest a possibility of protocatechuic acid to be a new therapeutic agent for DC in future.
Scientific reports, Jan 14, 2018
Eye irritation assessment is compulsory to anticipate health risks in military personnel exposed ... more Eye irritation assessment is compulsory to anticipate health risks in military personnel exposed to riot control agents such as capsaicin, the principal constituent of oleoresin capsicum, or pepper sprays. The present work investigates certain fundamental yet unaddressed pharmacological manifestations on ocular exposure to capsaicin. Ocular pharmacology of capsaicin was studied using acute eye irritation (AEI), bovine corneal opacity and permeability (BCOP) assay, corneal fluorescein staining and indirect ophthalmoscopy studies, transcorneal permeation, Schirmer tear secretion test, nerve conduction velocity study and enzyme-linked immunosorbent assay (ELISA). Additionally, histopathology and scanning electron microscopy (SEM) of bovine corneas and rat optic nerves were done to further estimate capsaicin induced morphological variations. Our findings demonstrated that AEI, BCOP, corneal fluorescein staining and indirect ophthalmoscopy were useful in assessing capsaicin induced ocula...
ACS omega, Jan 28, 2018
Engaging Raman spectroscopy as a primary tool, we investigated the early events of insulin fibril... more Engaging Raman spectroscopy as a primary tool, we investigated the early events of insulin fibrilization and determined the structural content present in oligomer and protofibrils that are formed as intermediates in the fibril formation pathway. Insulin oligomer, as obtained upon incubation of zinc-free insulin at 60 °C, was mostly spherical in shape, with a diameter of 3-5 nm. Longer incubation produced "necklace"-like beaded protofibrillar assembly species. These intermediates eventually transformed into 5-8 nm thick fibers with smooth surface texture. A broad amide I band in the Raman spectrum of insulin monomer appeared at 1659 cm, with a shoulder band at 1676 cm. This signature suggested the presence of major helical and extended secondary structure of the protein backbone. In the oligomeric state, the protein maintained its helical imprint (∼50%) and no substantial increment of the compact cross-β-sheet structure was observed. A nonamide helix signature band at 940 c...
European journal of pharmacology, Jan 15, 2018
Capsaicin is the principal constituent of oleoresin capsicum, or pepper spray, as it is commonly ... more Capsaicin is the principal constituent of oleoresin capsicum, or pepper spray, as it is commonly known. Pepper sprays are frequently used in riot control situations by defence organizations all over the world to deal with uncontrolled civil or criminal disturbances. Although capsaicin is noted for its irritant and inflammatory properties, the ocular profile of capsaicin has not been specifically studied and interpreted. The present review analyses the mammalian opthalmological profile of capsaicin and its pharmacological and toxicological manifestations including capsaicin induced corneal changes, neurogenic inflammation, neuroprotective influences on retinal ganglion cells (RGCs), depletion of neuropeptide content in sensory nerve terminals etc. Substantial views on the capsaicin receptor Transient Receptor Potential Vanilloid V1 (TRPV1), its presence, significance and capsaicin induced mediations have been presented. Studies conducted previously on the reversal of capsaicin evoked...
International Journal of Quantitative Structure-Property Relationships
The present approach has aimed to investigate the physicochemical and structural requirements of ... more The present approach has aimed to investigate the physicochemical and structural requirements of a molecule to impart potential and selective PPARa agonistic activity using various ligand-based and structure-based molecular modeling techniques. These studies suggest the presence oxo heterocyclic ring connected with lipophilic substituents (phenyl, flurophenyl or any hydropbic alkyl chain) may responsible for hydrophobic interaction with the receptor. Both regression-based and classification-based QSAR, and HQSAR models infer that the ether linkage is very crucial for the activity, where as long alkyl chain or acyclic ring and the chloride substituent have detrimental effects. The pharmacophore models strongly depict the presence of two acceptors and hydrophobic region are very much essential for promising activity. The docking and MD studies suggest the presence of carboxyl group is essential for H-bond interaction with catalytic residues. The cheminformatics study provides key info...
Medicinal Chemistry Research