Department of Biological Sciences
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Item 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 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 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.Item Synthesis and in-vitro anti-leishmanial activity of (4-arylpiperazin-1-yl)(1-(thiophen-2-yl)-9H-pyrido[3,4-b]indol-3-yl)methanone derivatives(Elsiever, 2017-02) Jha, Prabhat N.; Murugesan, SankaranarayananIn the present study, we have reported synthesis and biological evaluation of a series of fifteen 1-(thiophen-2-yl)-9H-pyrido[3,4-b]indole derivatives against both promastigotes and amastigotes of Leishmania parasites responsible for visceral (L. donovani) and cutaneous (L. amazonensis) leishmaniasis. Among these reported analogues, compounds 7b, 7c, 7f, 7g, 7i, 7j, 7m, 7o displayed potent activity (15.55, 7.70, 7.00, 3.80, 14.10, 9.25, 3.10, 4.85 μM, respectively) against L. donovani promastigotes than standard drugs miltefosine (15.70 μM) and pentamidine (32.70 μM) with good selectivity index. In further, in-vitro evaluation against amastigote forms, two compounds 7g (8.80 μM) and 7i (7.50 μM) showed significant inhibition of L. donovani amastigotes. Standard drug amphotericin B is also used as control to compare inhibition potency of compounds against both promastigote (0.24 μM) and amastigote (0.05 μM) forms.Item Biological evaluation and structure activity relationship of 9-methyl-1-phenyl-9H-pyrido[3,4-b]indole derivatives as anti-leishmanial agents(Elsiever, 2019) Jha, Prabhat N.; Murugesan, SankaranarayananA series of piperazinyl-β-carboline-3-carboxamide derivatives were designed through a molecular hybridization approach. Designed analogues were synthesized, characterized and evaluated for anti-leishmanial activity against Leishmania infantum and Leishmania donovani. In L. infantum inhibition assay, compounds 7d, 7g and 7c displayed potent inhibition of promastigotes (EC50 1.59, 1.47 and 3.73 µM respectively) and amastigotes (EC50 1.4, 1.9 and 2.6 µM respectively). SAR studies revealed that, para substitution of methoxy, chloro groups and methyl group on ortho position favored anti-leishmanial activity against L. infantum. Among these analogues 7d, 7h, 7n and 7g exhibited potent inhibition against L. donovani promastigotes (EC50 0.91, 4.0, 4.57 and 5.02 µM respectively), axenic amastigotes (EC50 0.9, 3.5, 2.2 and 3.8 µM respectively) and intracellular amastigotes (EC50 1.3, 7.8, 5.6 and 6.3 µM respectively). SAR studies suggested that, para substitution of methoxy group, para and meta substitution of chloro groups and benzyl replacement recommended for significant anti-leishmanial against L. donovani.