Abhinav Kanwal
Indian Institute of Chemical Technology
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Featured researches published by Abhinav Kanwal.
Analytical Biochemistry | 2012
Abhinav Kanwal; Shailendra Pratap Singh; Paramjit Grover; Sanjay K. Banerjee
Sodium-dependent glucose cotransporters (SGLT1 and SGLT2), which have a key role in the absorption of glucose in the kidney and/or gastrointestinal tract, have been proposed as a novel therapeutic strategy for diabetes and cardiomyopathy. Here we developed a simple cell-based, nonradioactive method for functional screening of SGLT1 and SGLT2 inhibitors. Stable cell lines expressing human SGLT1 and SGLT2 were established by transfecting HEK293 cells with vectors (pCMV6-Neo) having full-length human SGLT1 and SGLT2 and selecting the positive clones following neomycin treatment. We confirmed the gene expression of SGLT1 and SGLT2 by reverse transcription polymerase chain reaction (RT-PCR) and immunoblotting. Furthermore, to analyze the function of SGLTs, we incubated stable cell lines with 2-deoxyglucose or fluorescent d-glucose analog (2-NBDG) and performed glucose uptake assay. A significant (P<0.001) increase in glucose uptake was observed in both cell lines. The increased glucose uptake in both cell lines was completely inhibited when treated with nonspecific SGLT1/SGLT2 inhibitors and phlorizin (100μM), but not when treated with nonspecific sodium-independent facilitative glucose transporter (GLUT) inhibitors (100μM). Taken together, our data suggest that cell-based methods developed for screening SGLT1/SGLT2 inhibitors are phlorizin sensitive and specific for respective glucose transporters. This assay provides a simple and rapid method for identifying novel and selective SGLT inhibitors.
Neurobiology of Aging | 2015
Arpit Mehrotra; Abhinav Kanwal; Sanjay K. Banerjee; Rajat Sandhir
Huntingtons disease (HD) is a chronic neurodegenerative condition involving impaired mitochondrial functions. The present study evaluates the therapeutic potential of combined administration of mitochondrial modulators: alpha-lipoic acid and acetyl-l-carnitine on mitochondrial dysfunctions in 3-NP-induced HD. Our results reveal 3-NP administration resulted in compromise of mitochondrial functions in terms of: (1) impaired activity of mitochondrial respiratory chain enzymes, altered cytochrome levels, reduced histochemical staining of complex-II and IV, reduced in-gel activity of complex-I to V, and reduced mRNA expression of respiratory chain complexes; (2) enhanced mitochondrial oxidative stress indicated by increased malondialdehyde, protein carbonyls, reactive oxygen species and nitrite levels, along with decreased Mn-superoxide dismutase and catalase activity; (3) mitochondrial structural changes measured by mitochondrial swelling, reduced mitochondrial membrane potential and ultra-structure changes; (4) increased cytosolic cytochrome c levels, caspase-3 and -9 activity along with altered expression of apoptotic proteins (AIF, Bim, Bad, and Bax); and (5) impaired cognitive functions assessed using Morris water maze and Y-maze. Combination of mitochondrial modulators (alpha-lipoic acid + acetyl-l-carnitine) on the other hand ameliorated 3-NP-induced mitochondrial dysfunctions, oxidative stress, histologic alterations, and behavioral deficits, suggesting their therapeutic efficacy in the management of HD.
Pharmaceutical patent analyst | 2013
Abhinav Kanwal; Sanjay K. Banerjee
Inhibiting sodium-glucose co-transporters (SGLT1/SGLT2), which have a key role in the absorption of glucose in the kidney and/or GI tract has been proposed as a novel therapeutic strategy for diabetes. Thus, screening and patenting of chemical compounds for SGLT1/SGLT2 gets more importance in the development of new drugs in diabetes. Several companies are developing SGLT inhibitors, some of which are now in various stages of clinical development. Some molecules in the pipeline, including dapagliflozin, canagliflozin, ASP1941, BI10773, LX4211, RG7201 and TS071, are at various stages of drug development. This patent review presents the overall progress carried out in the development of SGLT inhibitors over the last decade with the active participation of various pharmaceutical companies. This class of drug is anticipated to have a large impact on diabetes field and predicting to attain a blockbuster status.
Bioorganic & Medicinal Chemistry | 2013
Dinesh Addla; Anvesh Jallapally; Abhinav Kanwal; Balasubramanian Sridhar; Sanjay K. Banerjee; Srinivas Kantevari
A series of novel 10-substituted 2-hydroxypyrrolobenzodiazepine-5,11-diones designed through structure based rational hybridization approach, synthesized by the cyclodehydration of isotonic anhydride with (2S,4R)-4-hydroxypyrrolidine-2-carboxylic acid followed by N-substitution, were evaluated as angiotensin converting enzyme (ACE) inhibitors. Among all the new compounds screened (2R,11aS)-10-((4-bromothiophen-2-yl)methyl)-2-hydroxy-2,3-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-5,11(10H,11aH)dione, 5v (IC₅₀: 0.272 μM) emerged as most active non-carboxylic acid ACE inhibitor with minimal toxicity comparable to clinical drugs Lisinopril, Benazepril and Ramipril. Favorable binding characteristics in docking studies also supported the experimental results.
Bioorganic & Medicinal Chemistry | 2014
Ravindra M. Kumbhare; Umesh B. Kosurkar; Pankaj K. Bagul; Abhinav Kanwal; K. Appalanaidu; Tulshiram L. Dadmal; Sanjay K. Banerjee
A series of novel diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate embedded triazole and mannich bases were synthesized, and evaluated for their angiotensin converting enzyme (ACE) inhibitory activity. Screening of above synthesized compounds for ACE inhibition showed that triazoles functionalized compounds have better ACE inhibitory activity compared to that of mannich bases analogues. Among all triazoles we found 6 h, 6 i and 6 j to have good ACE inhibition activity with IC50 values 0.713 μM, 0.409 μM and 0.653 μM, respectively. Among mannich bases series compounds, only 7c resulted as most active ACE inhibitor with IC50 value of 0.928 μM.
Bioorganic & Medicinal Chemistry Letters | 2014
Siddamal Reddy Putapatri; Abhinav Kanwal; Sanjay K. Banerjee; Srinivas Kantevari
Sodium-glucose co-transporter (SGLT) inhibitors are a novel class of therapeutic agents for the treatment of type 2 diabetes by preventing renal glucose reabsorption. In our efforts to identify novel inhibitors of SGLT, we synthesized a series of l-rhamnose derived acyclic C-nucleosides with 1,2,3-triazole core. The key β-ketoester building block 4 prepared from l-rhamnose in five steps, was reacted with various aryl azides to produce the respective 1,2,3-triazole derivatives in excellent yields. Deprotection of acetonide group gave the desired acyclic C-nucleosides 7a-o. All the new compounds were screened for their sodium-glucose co-transporters (SGLT1 and SGLT2) inhibition activity using recently developed cell-based nonradioactive fluorescence glucose uptake assay. Among them, 7m with IC50: 125.9nM emerged as the most potent SGLT2 inhibitor. On the other hand compound 7d exhibited best selectivity for inhibition of SGLT2 (IC50: 149.1nM) over SGLT1 (IC50: 693.2nM). The results presented here demonstrated the utility of acyclic C-nucleosides as novel SGLT inhibitors for future investigations.
Personalized Medicine | 2016
Ramu Adela; Soheb A. Mohammed; Abhinav Kanwal; Gayatri Vishwakarma; Podduturi Naveen Chander Reddy; Sanjay K. Banerjee
AIM Circulatory GDF-15, angiotensin II (Ang-II) and GDF-15 mRNA expression levels were examined in three groups, in other words, control (n = 25), Type 2 diabetes (T2DM; n = 25) and Type 2 diabetes with hypertension (T2DM_HTN; n = 36). RESULTS T2DM and T2DM_HTN subjects had significantly (p < 0.05) higher GDF-15 and Ang-II levels compared with control subjects. Significant positive correlation was found between Ang-II and GDF-15 levels. GDF-15 mRNA expression from blood cells was significantly elevated in T2DM_HTN (p < 0.05) but not in T2DM subjects. GDF-15 mRNA expression was significantly elevated in Ang-II-treated (50 nM) THP-1 (p < 0.001) and H9C2 (p < 0.05) cells but not altered after high glucose treatment. CONCLUSION Collectively, our data suggest that higher levels of GDF-15 is associated with increased Ang-II levels in diabetic patients with concurrent hypertension.
Drug Design Development and Therapy | 2016
Abhinav Kanwal; Sujatha Kasetti; Uday Kumar Putcha; Shailendra Asthana; Sanjay K. Banerjee
The concept of cardioprotection through preconditioning against ischemia–reperfusion (I/R) injury is well known and established. However, among different proposed mechanisms regarding the concept of ischemic preconditioning, protein kinase C (PKC)-mediated cardioprotection through ischemic preconditioning plays a key role in myocardial I/R injury. Thus, this study was designed to find the relationship between PKC and sodium glucose transporter 1 (SGLT1) in preconditioning-induced cardioprotection, which is ill reported till now. By applying a multifaceted approach, we demonstrated that PKC activates SGLT1, which curbed oxidative stress and apoptosis against I/R injury. PKC activation enhances cardiac glucose uptake through SGLT1 and seems essential in preventing I/R-induced cardiac injury, indicating a possible cross-talk between PKC and SGLT1.
Medicinal Chemistry Research | 2014
Sridhar Madabhushi; Narsaiah Chinthala; Abhinav Kanwal; Gagandeep Kaur; Sanjay K. Banerjee
Abstract2-(4-((1-Alkyl/aryl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)naphtho[1,2-d] were prepared and evaluated as protein tyrosine phosphatase 1B (PTP1B) inhibitors. In this study, two new compounds with potent PTP1B inhibitory activity were identified.
Molecular and Cellular Biochemistry | 2012
Bhavesh Sojitra; Yogesh Bulani; Uday Kumar Putcha; Abhinav Kanwal; Prachi Gupta; Madhusudana Kuncha; Sanjay K. Banerjee