BITS Faculty Publications
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Item Greener alternatives for synthesis of isoquinoline and its derivatives: a comparative review of eco-compatible synthetic routes(RSC, 2025) Deepa, P.R.; Murugesan, SankaranarayananIsoquinoline derivatives, a prominent class of nitrogen-containing heterocycles, serve a pivotal role in medicinal chemistry due to their broad spectrum of bioactivities. While traditional synthetic routes for these scaffolds are well-established, conventional methods often rely on transition-metal catalysts, harsh conditions, expensive reagents, and toxic solvents, raising environmental and economic concerns. In response to the pressing demand for sustainable practices, this review underscores the integration of green chemistry principles into modern synthetic design, offering environmentally acceptable methods for accessing isoquinoline frameworks. Despite extensive research on isoquinoline synthesis and its therapeutic relevance, a dedicated analysis of sustainable methodologies remains absent. This work bridges that gap by critically evaluating recent innovations in green synthesis, including the use of benign solvents, recyclable catalytic systems, atom-economical reactions, and energy-efficient processes.Item Targeting stearoyl-coa desaturase-1 (SCD1) by the drug–nutraceutical combination of montelukast and bixin in ameliorating steatotic NAFLD(ACS, 2025-10) Sharma, Pankaj Kumar; Murugesan, Sankaranarayanan; Deepa, P.RNonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome, which progresses from simple fat accumulation (steatosis) to nonalcoholic steatohepatitis (NASH), fibrosis, and eventually liver cancer. Stearoyl-CoA desaturase 1 (SCD1), a key lipogenic enzyme, plays a significant role in the progression of NAFLD by promoting the accumulation of fat in the liver. This study investigated the drug-nutraceutical combination of Montelukast (a synthetic anti-inflammatory drug) and Bixin (an apo-carotenoid) as SCD1 inhibitors for treating fatty liver disease. Bixin was identified through virtual screening of a curated carotenoid database (carotenoid DB) targeting lipogenic enzyme SCD1. In the in vitro model of steatotic HepG2 cells, the combination treatment of Montelukast and Bixin showed a marked reduction (P < 0.05) in SCD1 gene expression (41%), protein expression (61%), and SCD1 enzyme activity (56.22%). The combination treatment showed a significant reduction of 21.64% (P < 0.05) in lipid accumulation relative to individual treatment with Bixin or Montelukast and was comparable with the reference drug Aramchol (21.83%). The markers of oxidative stress were also significantly reduced (P < 0.05), evidenced by decreased MDA (42.25%), RNS levels (32.59%), and ROS levels (30.72%) in the combination group. These findings suggest that Bixin and Montelukast in combination hold potential for managing the multiple aspects in the pathophysiology of NAFLD development and progression.Item Unraveling PPARβ/δ nuclear receptor agonists via a drug-repurposing approach: HTVS-based ligand identification, molecular dynamics, pharmacokinetics, and in vitro anti-steatotic validation(RSC, 2025-04) Sharma, Pankaj Kumar; Murugesan, Sankaranarayanan; Deepa, P.R.Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors with a crucial regulatory role in carbohydrate and lipid metabolism and are emerging druggable targets in “metabolic syndrome” (MetS) and cancers. However, there is a need to identify ligands that can activate specific PPAR subtypes, particularly PPARβ/δ, which is less studied compared with other PPAR isoforms (α and γ). Herein, using the drug-repurposing approach, the ZINC database of clinically approved drugs was screened to target the PPARβ/δ receptor through high-throughput-virtual-screening, followed by molecular docking and molecular dynamics (MD) simulation. The top-scoring ligands were subjected to drug-likeness analysis. The hit molecule was tested in an in vitro model of NAFLD (non-alcoholic fatty liver disease). The top five ligands with strong binding affinity towards PPARβ/δ were canagliflozin > empagliflozin > lumacaftor > eprosartan > dapagliflozin. RMSD/RMSF analysis demonstrated stable protein–ligand complexation (PLC) by the top-scoring ligands with PPARβ/δ. In silico ADMET prediction analysis revealed favorable pharmacokinetic profiles of these top five ligands. Canagliflozin showed significant (P < 0.001) dose-dependent decrease in lipid accumulation and the associated oxidative stress-inflammatory response, suggesting its promising anti-steatotic potential. These outcomes pave the way for further validation and development of PPAR activity-modulating therapeuticsItem Metal-free, visible-light-mediated synthesis of tetracyclic benzimidazole: regioselective c–h functionalization with in vitro and computational study of anti-breast cancer compounds(ACS, 2025-02) Murugesan, Sankaranarayanan; Mukherjee, SudeshnaGlobally, breast cancer is the leading cause of mortality. Within the field of antibreast cancer drug design by several compound docking studies, eight new N-containing nonsteroid tetracyclic derivatives have been synthesized via regioselective intramolecular C–H functionalization by visible light. The adopted methodology is highly efficient, green, and sustainable to unload a new pathway with excellent yield. It offers a rapid, low-cost, catalyst-free method for creating physiologically active molecules from easily accessible substrates. The synthesized substances were described using spectroscopic methods like HRMS, 1HNMR, 13CNMR, and XRD analysis. This study explores the cytotoxic potential of novel compounds against human MCF-7 breast cancer cells. This study includes in vitro experiments to assess the effect of our compounds on cells. These experiments include cytotoxicity assessment by cell cycle, apoptosis, MTT test analysis by flow cytometry, reactive oxygen species (ROS) production assessment, etc. Among the novel compounds, compound 2e exhibited the most potent cytotoxic activity, with an inhibitory concentration (IC50) of 40 nM, surpassing the efficacy of established drugs such as exemestane (IC50 24.97 micromolar) and tamoxifen (IC50 5.45 μM). Compound 2e also significantly induced apoptosis and cell cycle arrest in the G1 phase, increasing the apoptotic cell population to 65.97%. Additionally, the compound led to a marked rise in the level of ROS generation, implicating oxidative stress in its mechanism of action. Molecular docking and dynamic simulation further supported the vigorous anticancer activity of compound 2e, demonstrating its promise as an effective breast cancer treatment.Item In silico and in vitro analysis of PPAR – α / γ dual agonists: Comparative evaluation of potential phytochemicals with anti-obesity drug orlistat(Elsevier, 2022) Deepa, P.R.; Sharma, Pankaj Kumar; Murugesan, SankaranarayananObesity is an abnormal fat accumulation disorder in the metabolic syndrome constellation, and a risk factor for diabetes, cardiovascular disorders, non-alcoholic fatty liver disease (NAFLD), and cancer. Nuclear receptors (Peroxisome proliferator-activated receptor, PPAR) are implicated in metabolic syndrome and NAFLD, and have potential for therapeutic targeting. Nuclear receptors are ligand-dependent transcription factors that have diverse roles in metabolism, including regulating genes involved in lipid and glucose metabolism, modulating inflammatory genes, and are crucial for maintaining metabolic flexibility. PPAR activates adipose triglyceride lipase, which then releases fatty acids as ligands for PPAR, indicating the interdependency of nuclear receptors and lipases. Here, molecular docking was performed with selected phytochemical ligands that can bind with PPAR-α/γ (PDB ID: 2ZNN and 2ATH, respectively) using Glide module of Schrodinger software followed by molecular dynamics simulation study using Desmond module, and ADMET analysis. Interestingly, orlistat which is a well-known lipase and fatty acid synthase inhibitor also demonstrated favorable binding affinity with both PPAR-α/γ (−10.96 kcal/mol against PPARα and −10.26 kcal/mol against PPARγ). The highest docking scores were however shown by the flavonoids - rutin (−14.88 kcal/mol against PPARα and −13.64 kcal/mol against PPARγ), and its aglycone, quercetin (−10.08 kcal/mol in PPARα and −9.89 kcal/mol in PPARγ). The other phytochemicals (genistein, esculin, daidzin, naringenin, daidzein, dihydroxy coumarin, hydroquinone) showed lower binding affinity as dual agonists. The anti-obesity effects were experimentally validated in cultured adipocytes, which revealed better lipid inhibition by rutin and quercetin than orlistat (quercetin > rutin > orlistat) pointing to their strong potential in anti-obesity treatment.Item Targeting lipid-sensing nuclear receptors PPAR (α, γ, β/δ): HTVS and molecular docking/dynamics analysis of pharmacological ligands as potential pan-PPAR agonists(Springer, 2023-06) Deepa, P.R.; Sharma, Pankaj Kumar; Murugesan, SankaranarayananThe global prevalence of obesity-related systemic disorders, including non-alcoholic fatty liver disease (NAFLD), and cancers are rapidly rising. Several of these disorders involve peroxisome proliferator-activated receptors (PPARs) as one of the key cell signaling pathways. PPARs are nuclear receptors that play a central role in lipid metabolism and glucose homeostasis. They can activate or suppress the genes responsible for inflammation, adipogenesis, and energy balance, making them promising therapeutic targets for treating metabolic disorders. In this study, an attempt has been made to screen novel PPAR pan-agonists from the ZINC database targeting the three PPAR family of receptors (α, γ, β/δ), using molecular docking and molecular dynamics (MD) simulations. The top scoring five ligands with strong binding affinity against all the three PPAR isoforms were eprosartan, canagliflozin, pralatrexate, sacubitril, olaparib. The ADMET analysis was performed to assess the pharmacokinetic profile of the top 5 molecules. On the basis of ADMET analysis, the top ligand was subjected to MD simulations, and compared with lanifibranor (reference PPAR pan-agonist). Comparatively, the top-scoring ligand showed better protein–ligand complex (PLC) stability with all the PPARs (α, γ, β/δ). When experimentally tested in in vitro cell culture model of NAFLD, eprosartan showed dose dependent decrease in lipid accumulation and oxidative damage. These outcomes suggest potential PPAR pan-agonist molecules for further experimental validation and pharmacological development, towards treatment of PPAR-mediated metabolic disorders.Item Design, in silico modeling, biodistribution study of rutin and quercetin loaded stable human hair keratin nanoparticles intended for anticancer drug delivery(IOP, 2018) Chowdhury, Rajdeep; Murugesan, SankaranarayananCurrent drug development using functional polymers is one of the major tasks for enhancing effectiveness and reducing the side effects in cancer therapeutics. To achieve this immense goal, human hair keratin and model drugs rutin-quercetin (Ru-Qr) were chosen to formulate nanoparticles (NPs). Drug delivery is a core path to produce significant biological activity, and in this connection, the current study was designed to produce highly stable Ru-Qr NPs and their characterization such as the encapsulation of Ru-Qr, the nature, molecular shape, particle size, stability and polydispersity index by Fourier transform infrared spectroscopy, x-ray diffraction, scanning electron microscopy, transmission electron microscopy and Zetasizer analyzer. Based on a literature report, the drug targets 521P and 5P21 were chosen to perform in silico study. The observed in silico study reports showed the strong interaction of NPs and binding pockets of H-Ras P21 proto-oncogene. In this respect, the importance of NPs prompted us to study the biodistribution and in vitro anticancer activity by using cancer cell lines. The investigation of biodistribution showed that it penetrated after 3 d of injection, up to 14% in the liver, 18% in the kidneys, 8% in the spleen, 3% in the heart and 0% in the brain. At 50 μg ml−1 concentration, the NPs displayed 78.02% viability in the normal liver cell line and 95.60% cytotoxicity in the HeLa cell line. The obtained results showed the active NPs enhancing controlled, site-specific drug delivery and they can serve as a novel nanodrug in the management of cancer.Item A Rapid, Green, Efficient Microwave-Assisted Synthesis and Antimicrobial Activity of Novel Glycinamide of 6,7-Dimethoxy-1, 2, 3, 4-Tetrahydroisoquinolines(Bentham Science, 2015) Jha, Prabhat N.; Murugesan, SankaranarayananA reliable, green and energy-efficient synthesis of a series of 1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)- yl)-2-(phenylamino)ethanone is reported. The reaction conditions were optimized using the conventional and microwave synthetic approaches. The un-precedented displacement of the chloro group of 2-chloro-1-(6,7-dimethoxy-3,4- dihydroisoquinolin-2(1H)-yl)ethanone with substituted anilines under microwave solvent free condition afforded titled glycinamides in moderate to good yield (66-84 %) in a short reaction time (3-4.5 min). All the synthesized compounds were evaluated for in vitro antibacterial activity against three bacterial strains Escherichia coli, Pseudomonas putida and Staphylococcus aureus. Among all the tested compounds, four compounds 5c, 5f, 5i and 5k exhibited moderate to significant activity against all the three tested strains of bacteria.Item Synthesis, evaluation and molecular docking studies of amino acid derived N-glycoconjugates as antibacterial agents(Elsiever, 2015-12) Jha, Prabhat N.; Sah, Ajay Kumar; Murugesan, SankaranarayananSix amino acid derived N-glycoconjugates of d-glucose were synthesized, characterized and tested for antibacterial activity against G(+)ve (Bacillus cereus) as well as G(−)ve (Escherichia coli and Klebsiella pneumoniae) bacterial strains. All the tested compounds exhibited moderate to good antibacterial activity against these bacterial strains. The results were compared with the antibacterial activity of standard drug Chloramphenicol, where results of A5 (Tryptophan derived glycoconjugates) against E. coli and A4 (Isoleucine derived glycoconjugates) against K. pneumoniae bacterial strains are comparable with the standard drug molecule. In silico docking studies were also performed in order to understand the mode of action and binding interactions of these molecules. The docking studies revealed that, occupation of compound A5 at the ATP binding site of subunit GyrB (DNA gyrase, PDB ID: 3TTZ) via hydrophobic and hydrogen bonding interactions may be the reason for its significant in vitro antibacterial activity.Item Rational Design, Synthesis, Anti-HIV-1 RT and Anti-microbial Activity of Novel 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-phenylpropanamide Derivatives(Bentham Science, 2016) Jha, Prabhat N.; Murugesan, SankaranarayananBackground: AIDS continues to be a major public health issue worldwide. In 2014, an estimated 36.9 million people were living with HIV, in the same year, around 1.2 million people died due to AIDS-related illnesses. Due to global efforts particularly made in the last decade has reduced mortality rate due to AIDS and associated diseases. But still many people living with HIV/AIDS particularly in the low and middle income countries do not have access of anti-HIV drugs. Moreover, still there is no permanent cure of disease and rapid emergence of drug resistance by HIV towards the current available therapy further drive the need for the search of new potential anti- HIV drugs. Methods: In the present study, fifteen novel 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-phenylpropanamide derivatives (5a-o) were designed as HIV-1 Reverse Transcriptase (RT) inhibitors, in-silico evaluated for drug likeness behaviour, synthesized and characterized. Compounds were evaluated in-vitro for inhibition of HIV-1 RT activity. Three compounds (5a, 5f and 5o) as representative of the series were evaluated for cytotoxicity studies on human T lymphocytes (C8166 cells). All the synthesized compounds were also evaluated for in-vitro antibacterial (E. coli, P. putida, S. aureus and B. cereus) and antifungal (C. albicans and A. niger) activity. Results: All compounds (5a-o) possessed drug-likeness behavior based upon their in-silico predicted drug-likeness properties. Five compounds 5f, 5h, 5i, 5k and 5n exhibited more than 50% inhibition of HIV-1 RT, in which compound 5h showed highest inhibition (61%). Cytotoxicity studies of compounds 5a, 5f and 5o on T lymphocytes revealed that, all three exhibited CC50 >200 µg/ml. Four compounds 5f, 5i, 5j and 5n showed significant inhibition against the tested G(-) ve (E. coli and P. putida) bacterial strains while one compound 5f significantly inhibited the growth of all tested bacterial strains. Among the series, four compounds (5e, 5f, 5i and 5m) significantly inhibited the growth of A. niger, while compound 5m exhibited significant inhibition of both the tested fungal strains. Conclusion: Titled compounds (5a-o) exhibited weak to significant inhibition of HIV-1 RT, particularly 5h. Four compounds showed significant anti-bacterial activity against the both tested G(-)ve bacterial strains, moreover compound 5f significantly inhibited the growth of all four tested bacterial strains. Four compounds significantly inhibited the growth of A. niger, in which compound 5m exhibited significant inhibition of both the tested fungal strains.