SAI Life science Ltd.

Turkapally, India

SAI Life science Ltd.

Turkapally, India

Time filter

Source Type

Jin C.H.,Ewha Womans University | Krishnaiah M.,Ewha Womans University | Sreenu D.,Ewha Womans University | Sreenu D.,Sai Life science Ltd. | And 11 more authors.
Journal of Medicinal Chemistry | Year: 2014

A series of 2-substituted-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6- methylpyridin-2-yl)imidazoles was synthesized and evaluated to optimize a prototype inhibitor of TGF-β type I receptor kinase (ALK5), 6. Combination of replacement of a quinoxalin-6-yl moiety of 6 with a [1,2,4]triazolo[1,5-a] pyridin-6-yl moiety, insertion of a methyleneamino linker, and a o-F substituent in the phenyl ring markedly increased ALK5 inhibitory activity, kinase selectivity, and oral bioavailability. The 12b (EW-7197) inhibited ALK5 with IC50 value of 0.013 μM in a kinase assay and with IC50 values of 0.0165 and 0.0121 μM in HaCaT (3TP-luc) stable cells and 4T1 (3TP-luc) stable cells, respectively, in a luciferase assay. Selectivity profiling of 12b using a panel of 320 protein kinases revealed that it is a highly selective ALK5/ALK4 inhibitor. Pharmacokinetic study with 12b·HCl in rats showed an oral bioavailability of 51% with high systemic exposure (AUC) of 1426 ng × h/mL and maximum plasma concentration (Cmax) of 1620 ng/mL. Rational optimization of 6 has led to the identification of a highly potent, selective, and orally bioavailable ALK5 inhibitor 12b. © 2014 American Chemical Society.


Nalwade S.,Andhra University | Nalwade S.,SAI Life science Ltd. | Reddy V.R.,Dr. Reddys Laboratories Ltd. | Kulkarni D.,SAI Life science Ltd. | Todamal S.,SAI Life science Ltd.
Journal of Chromatographic Science | Year: 2015

A novel, sensitive, stability-indicating, gradient, reverse-phase highperformance liquid chromatographic method has been developed for quantitative determination of halobetasol propionate and its impurities in topical dosage forms. The chromatographic separation was achieved on a Phenomenex Synergi polar reverse phase, 250 × 4.6 mm, 4 μm column. Mobile phase A comprises a mixture of 0.01 M KH2PO4 buffer containing 0.2% 1-octane sulfonic acid sodium salt (pH 3.0), acetonitrile and methanol in the ratio 80:15:05 (v/v/v), respectively, and mobile phase B contains a mixture of 0.01 M KH2PO4 buffer containing 0.2% 1-octane sulfonic acid sodium salt (pH 3.0), acetonitrile and methanol in the ratio 20:70:10 (v/v/v), respectively. The flow rate is 0.8 mL min-1. The column compartment temperature is set at 40°C and the detection wavelength is set at 240 nm. The resolutions between Halobetasol propionate and all the impurities are >2.0 for all pairs of compounds. The drug product was subjected to International Conference on Harmonization (ICH)-prescribed hydrolytic, oxidative, photolytic and thermal stress conditions. The method is validated as per the ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision, robustness and ruggedness. © The Author [2014]. Published by Oxford University Press. All rights reserved.


Shirude P.S.,Astrazeneca | Shirude P.S.,Sai Life science Ltd | Shandil R.K.,Astrazeneca | Manjunatha M.R.,Astrazeneca | And 23 more authors.
Journal of Medicinal Chemistry | Year: 2014

In a previous report, we described the discovery of 1,4-azaindoles, a chemical series with excellent in vitro and in vivo antimycobacterial potency through noncovalent inhibition of decaprenylphosphoryl-β-d-ribose-2′- epimerase (DprE1). Nevertheless, high mouse metabolic turnover and phosphodiesterase 6 (PDE6) off-target activity limited its advancement. Herein, we report lead optimization of this series, culminating in potent, metabolically stable compounds that have a robust pharmacokinetic profile without any PDE6 liability. Furthermore, we demonstrate efficacy for 1,4-azaindoles in a rat chronic TB infection model. We believe that compounds from the 1,4-azaindole series are suitable for in vivo combination and safety studies. © 2014 American Chemical Society.


Malkapuram S.,Sai Life science Ltd | Venkataraman K.,Vellore Institute of Technology | Tongaonkar R.,Sai Life science Ltd | Taran S.,Sai Life science Ltd | And 2 more authors.
Research Journal of Medicinal Plant | Year: 2016

Green Coffee Extract (GCE), an extract of Coffea arabica bean is a popular health supplement employed for anti-obesity and anti-diabetic effects. Here a hydroalcoholic extract of Green Coffee (GCE) was evaluated for its potential as a cardioprotective agent against Doxorubicin (Dox) induced cardiac insult in a H9C2 rat cardiomyocyte in vitro model system. The GCE was tested in an MTT viability assay using 1 μM Dox with and without GCE pretreatment at 50, 100 and 250 μg mL-1 concentrations. GCE was also tested for its free radical scavenging ability in a DPPH assay at 10 concentrations (500 μg mL-1 maximum concentration). To understand the mechanism of action of cardioprotection, mitochondrial membrane potential (Δψm) was compared between Dox treated cells with and without GCE pretreatment, using the JC-1 dye. Finally, the activation of caspase-3/7 was quantitated. Findings from the above experiments demonstrated that GCE rescued H9C2 cardiomyocytes from Dox induced loss of cell viability in a dose-dependent manner. While Dox treatment caused a clear decrease in the JC-1 ratio from 2 to 1.6 due to loss of Δψm, pre- treatment with GCE at 25, 50 and 100 μg mL-1 restored the JC-1 ratio to 1.6, 1.9 and 2.0, respectively. Dox treatment potently induced caspase 3/7 activity by 5 fold and pre-treatment with GCE at 100 and 500 μg mL-1 reduced this activation to 3.5 and 1.5 fold, respectively. This data clearly demonstrates that GCE is strongly cardioprotective against Dox induced cardiac insult and the mechanism of action is by blocking activation of intrinsic apoptotic pathway. © 2016 Academic Journals Inc.


Pisal P.B.,Bharati Vidyapeeth Deemed University | Joshi M.A.,Sai Life science Ltd. | Padamwar M.N.,Sai Life science Ltd. | Patil S.S.,Bharati Vidyapeeth Deemed University | Pokharkar V.B.,Bharati Vidyapeeth Deemed University
International Journal of Pharmaceutics | Year: 2014

In the present work comparative evaluation of acetate and pH gradient techniques for effective drug loading in liposomes has been investigated. The acetazolamide (ACZ) loaded liposomes prepared by two methods were analyzed by vesicle size analysis, zeta potential, percent encapsulation efficiency, in vitro drug release studies and intraocular pressure lowering activity. ICH guidelines were followed for determining stability of the prepared liposomes. The superiority of acetate gradient method for active loading of acetazolamide has been established. The prepared acetate gradient positive liposomes showed extended hypotensive effect when compared to other liposomal formulations. Thus ACZ loaded liposomes prepared by acetate gradient technique may serve as promising ocular delivery system in the treatment of glaucoma. The current work emphasizes the fact that the techniques used for active drug loading into liposomes strongly influence the pharmaceutical performance of the final formulation. © 2002 The Royal Society of Chemistry.


Surve P.,Sai Life science Ltd | Ravindran S.,Sai Life science Ltd | Acharjee A.,Sai Life science Ltd | Rastogi H.,Sai Life science Ltd | And 2 more authors.
Drug Metabolism Letters | Year: 2013

Intensive Biotransformation studies on Gefitinib could play a significant role in designing and synthesizing new drugs around the core structure of Gefitinib. These studies may be useful in developing an entirely new drug by blocking the metabolic spots in Gefitinib. Gefitinib (Iressa) was the first oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Gefitinib shows toxicity to cancer cells and has the capability to inhibit the growth of cancer cells. Gefitinib is considered as one of the selective EGFR inhibitors to be available in clinical practice. In 2003, FDA had approved Gefitinib for metastatic non-small-cell lung cancer therapy (NSCLC). However, it was observed that NSCLC Patients who responded to treatment developed resistance to Gefitinib. Hence, in the present study Gefitinib was incubated with hepatocytes to identify both phase-I and Phase-II metabolites. Identified Phase -I metabolites were due to oxidative defluorination, N-dealkylation and loss of morpholine ring. One of the phase-II metabolites identified i.e. the glutathione adduct suggests the need to modify the structure of the drug for higher potency and safety.


Ravindran S.,Sai Life science Ltd | Basu S.,Sai Life science Ltd | Gorti S.K.K.,Sai Life science Ltd | Surve P.,Sai Life science Ltd | Sloka N.,Sai Life science Ltd
Biomedical Chromatography | Year: 2013

The sulfonylurea urea drug glyburide (glibenclamide) is widely used for the treatment of diabetes milletus and gestational diabetes. In previous studies monohydroxylated metabolites were identified and characterized for glyburide in different species, but the metabolite owing to the loss of cyclohexyl ring was identified only in mouse. Glyburide upon incubation with hepatic microsomes resulted in 10 metabolites for human. The current study identifies new metabolites of glyburide along with the hydroxylated metabolites that were reported earlier. The newly identified drug metabolites are dihydroxylated metabolites, a metabolite owing to the loss of cyclohexyl ring and one owing to hydroxylation with dehydrogenation. Among the 10 identified metabolites, there were six monohydroxylated metabolites, one dihydroxylated metabolite, two metabolites owing to hydroxylation and dehydrogenation, and one metabolite owing to the loss of cyclohexyl ring. New metabolites of glyburide were identified and characterized using liquid chromatography-diode array detector-quadruple-ion trap-mass spectrometry/mass spectrometry (LC-DAD-Q-TRAP-MS/MS). An enhanced mass scan-enhanced product ion scan with information-dependent acquisition mode in a Q-TRAP-MS/MS system was used to characterize the metabolites. Liquid chromatography with diode array detection was used as a complimentary technique to confirm and identify the metabolites. Metabolites formed in higher amounts were detected in both diode array detection and mass spectrometry detection. © 2012 John Wiley & Sons, Ltd.


PubMed | Bharati Vidyapeeth Deemed University and Sai Life science Ltd
Type: Comparative Study | Journal: International journal of pharmaceutics | Year: 2014

In the present work comparative evaluation of acetate and pH gradient techniques for effective drug loading in liposomes has been investigated. The acetazolamide (ACZ) loaded liposomes prepared by two methods were analyzed by vesicle size analysis, zeta potential, percent encapsulation efficiency, in vitro drug release studies and intraocular pressure lowering activity. ICH guidelines were followed for determining stability of the prepared liposomes. The superiority of acetate gradient method for active loading of acetazolamide has been established. The prepared acetate gradient positive liposomes showed extended hypotensive effect when compared to other liposomal formulations. Thus ACZ loaded liposomes prepared by acetate gradient technique may serve as promising ocular delivery system in the treatment of glaucoma. The current work emphasizes the fact that the techniques used for active drug loading into liposomes strongly influence the pharmaceutical performance of the final formulation.


PubMed | Sai Life science Ltd
Type: Journal Article | Journal: Biomedical chromatography : BMC | Year: 2013

The sulfonylurea urea drug glyburide (glibenclamide) is widely used for the treatment of diabetes milletus and gestational diabetes. In previous studies monohydroxylated metabolites were identified and characterized for glyburide in different species, but the metabolite owing to the loss of cyclohexyl ring was identified only in mouse. Glyburide upon incubation with hepatic microsomes resulted in 10 metabolites for human. The current study identifies new metabolites of glyburide along with the hydroxylated metabolites that were reported earlier. The newly identified drug metabolites are dihydroxylated metabolites, a metabolite owing to the loss of cyclohexyl ring and one owing to hydroxylation with dehydrogenation. Among the 10 identified metabolites, there were six monohydroxylated metabolites, one dihydroxylated metabolite, two metabolites owing to hydroxylation and dehydrogenation, and one metabolite owing to the loss of cyclohexyl ring. New metabolites of glyburide were identified and characterized using liquid chromatography-diode array detector-quadruple-ion trap-mass spectrometry/mass spectrometry (LC-DAD-Q-TRAP-MS/MS). An enhanced mass scan-enhanced product ion scan with information-dependent acquisition mode in a Q-TRAP-MS/MS system was used to characterize the metabolites. Liquid chromatography with diode array detection was used as a complimentary technique to confirm and identify the metabolites. Metabolites formed in higher amounts were detected in both diode array detection and mass spectrometry detection.


PubMed | Cancer Research UK Research Institute and SAI Life science Ltd
Type: Journal Article | Journal: Bioorganic & medicinal chemistry letters | Year: 2016

We have previously reported a series of anilinoquinazoline derivatives as potent and selective biochemical inhibitors of the RET kinase domain. However, these derivatives displayed diminished cellular potency. Herein we describe further optimisation of the series through modification of their physicochemical properties, delivering improvements in cell potency. However, whilst cellular selectivity against key targets could be maintained, combining cell potency and acceptable pharmacokinetics proved challenging.

Loading SAI Life science Ltd. collaborators
Loading SAI Life science Ltd. collaborators