Faculty Publications
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Item Synthesis, chemical characterization of novel 1,3-dimethyl acridones as cytotoxic agents, and their DNA-binding studies(2010) Sathish, N.K.; Gopkumar, P.; Rajendra Prasad, V.V.S.; Shanta Kumar, S.M.; Mayur, Y.C.A series of new 1,3-dimethyl acridone derivatives were synthesized with different alkyl side chain (propyl and butyl) substitution at N 10-position and highly basic amine groups at terminal end of alkyl side chain. All the synthesized molecules were screened for their cytotoxic activity against human breast adenocarcinoma (MCF-7) and human promyelocytic leukemia (HL-60) cell lines. DNA binding constants (Ki) of selected compounds were determined with calf-thymus DNA. Results showed that the molecules 7, 8, 10, 11, 12, 13, 14, and 15 exhibited good cytotoxic activity with IC50 value <10 ?M. Compound 14 having (?- hydroxyethyl) piperazine butyl side chain exhibited potent cytotoxic activity against MCF-7 cell line and DNA-intercalating properties. Examination of the relationship between lipophilicity and acridone derivatives showed poor correlation. © Birkhäuser Boston 2009.Item Synthesis, characterization and in vitro cytotoxic properties of some new Schiff and Mannich bases in Hep G2 cells(Birkhauser Boston, 2011) Dhanya, D.; Isloor, A.M.; Shetty, P.; Chandrakantha, B.; Satyamoorthy, K.A series of 5-substituted-4-amino-3-mercapto- 1,2,4-triazoles were synthesized and were treated with various 3-substituted pyrazole aldehydes to obtain a series of new Schiff bases (3a-l). Few of the selected Schiff bases were converted into Mannich bases by reaction with diphenylamine/morpholine in presence of formaldehyde in ethanol media (4a-e, 5a-e). These newly synthesized compounds were characterized by elemental analysis, IR, NMR and mass spectrometry studies. A comparative study on the cytotoxic activities of few selected Schiff and Mannich bases was done in HepG2 cells using MTT assay. Few of the screened Schiff bases, 3a, 3d, 3e, 3g and 3h showed dose dependent cytotoxic activity, 3a being the most potent with an IC50 value of 0.018 g/l comparable to the standard drug doxorubicin. Among the Mannich bases, 5b was the most active with an IC50 value of 0.034 g/l. The Schiff bases were found to be more active, when compared to Mannich bases derived from them. The morpholine derived Mannich bases were more potent than those obtained from diphenyl amine. © Springer Science+Business Media, LLC 2010.Item Synthesis, characterization, anticancer, and antioxidant activity of some new thiazolidin-4-ones in MCF-7 cells(2013) Isloor, A.M.; Dhanya, D.; Shetty, P.; Malladi, S.; Pai, K.S.R.; Maliyakkal, N.There are limited studies centring on the potential of thiazolidin-4-ones as anticancer agents. In this study, a new series of 2-(3-substituted-1H- pyrazol-4-yl)-3-(3-substituted-5-sulfanyl-1,2,4-triazol-4-yl)-1, 3-thiazolidin-4-one (4a-o) have been synthesized by cyclo-condensation reaction of 5-substituted-4-[(3-substituted-1H-pyrazol-4-ylmethylidene)amino]-2H-1,2,4- triazole-3-thione (3a-o) and thioglycolic acid. The structures of all the synthesized compounds were confirmed by elemental analysis, spectral techniques like IR, 1H NMR, and mass spectroscopy. Few compounds exhibited dose-dependent cytotoxic effect in MTT assay in human breast cancer (MCF-7) cells. Apoptotic degradation of DNA due to action of potent thiazolidin-4-ones was analysed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). A concentration-dependent increase in tail length and olive tail moment was observed when treated with thiazolidin-4-ones. In vitro antioxidant studies like DPPH and ABTS-free radical scavenging assays-indicated moderate activity of thiazolidin-4-ones. © 2012 Springer Science+Business Media, LLC.Item Identification and characterization of novel indole based small molecules as anticancer agents through SIRT1 inhibition(2013) Panathur, N.; Udayakumar, U.; Koushik, P.V.; Alvala, M.; Yogeeswari, P.; Sriram, D.; Kumar, V.In our pursuit to develop new potential anticancer leads, we designed a combination of structural units of indole and substituted triazole; and a library of 1-{1-methyl-2-[4-phenyl-5-(propan-2-ylsulfanyl)-4H-1,2,4-triazol-3- yl]-1H-indol-3-yl}methanamine derivatives was synthesized and characterized. Cytotoxic evaluations of these molecules over a panel of three human cancer cell lines were carried out. Few molecules exhibited potent growth inhibitory action against the treated cancer cell lines at lower micro molar concentration. An in vitro assay investigation of these active compounds using recombinant human SIRT1 enzyme showed that one of the compounds (IT-14) inhibited the deacetylation activity of the enzyme. The in vivo study of IT-14 exemplified its promising action by reducing the prostate weight to the body weight ratio in prostate hyperplasia animal models. A remarkable decrease in the disruption of histoarchitecture of the prostate tissues isolated from IT-14 treated animal compared to that of the positive control was observed. The molecular interactions with SIRT1 enzyme were also supported by molecular docking simulations. Hence this compound can act as a lead molecule to treat prostatic hyperplasia. © 2013 Elsevier Masson SAS. All rights reserved.Item Characteristics of airborne bacteria in Mumbai urban environment(Elsevier, 2014) Gangamma, S.Components of biological origin constitute small but a significant proportion of the ambient airborne particulate matter (PM). However, their diversity and role in proinflammatory responses of PM are not well understood. The present study characterizes airborne bacterial species diversity in Mumbai City and elucidates the role of bacterial endotoxin in PM induced proinflammatory response in ex vivo. Airborne bacteria and endotoxin samples were collected during April-May 2010 in Mumbai using six stage microbial impactor and biosampler. The culturable bacterial species concentration was measured and factors influencing the composition were identified by principal component analysis (PCA). The biosampler samples were used to stimulate immune cells in whole blood assay. A total of 28 species belonging to 17 genera were identified. Gram positive and spore forming groups of bacteria dominated the airborne culturable bacterial concentration. The study indicated the dominance of spore forming and human or animal flora derived pathogenic/opportunistic bacteria in the ambient air environment. Pathogenic and opportunistic species of bacteria were also present in the samples. TNF-? induction by PM was reduced (35%) by polymyxin B pretreatment and this result was corroborated with the results of blocking endotoxin receptor cluster differentiation (CD14). The study highlights the importance of airborne biological particles and suggests need of further studies on biological characterization of ambient PM. © 2014 Elsevier B.V.Item New indole-isoxazolone derivatives: Synthesis, characterisation and in vitro SIRT1 inhibition studies(Elsevier Ltd, 2015) Panathur, N.; Gokhale, N.; Udayakumar, U.; Koushik, P.V.; Yogeeswari, P.; Sriram, D.A new series of indole-isoxazolone hybrids bearing substituted amide, substituted [(1,2,3-triazol-4-yl)methoxy]methyl group or substituted benzylic ether at position-2 of the indole nucleus was synthesised using a facile synthetic route and the molecules were characterised using spectroscopic techniques. The molecules were screened against three human cancer cell lines to evaluate their in vitro cytotoxic property. Most of the trifluoromethyl substituted derivatives exhibited better growth inhibition activity than their methyl substituted analogues. The SIRT1 inhibition activity of two potent molecules (I17 and I18) was investigated and the SIRT1 IC50 values are 35.25 and 37.36 ?M, respectively for I17 and I18. The molecular docking studies with SIRT1 enzyme revealed favourable interactions of the molecule I17 with the amino acids constituting the receptor enzyme. © 2015 Elsevier Ltd. All rights reserved.Item Synthesis of novel 5-[(1,2,3-triazol-4-yl)methyl]-1-methyl-3H-pyridazino[4,5-b]indol-4-one derivatives by click reaction and exploration of their anticancer activity(Birkhauser Boston, 2016) Panathur, N.; Gokhale, N.; Udayakumar, U.; Koushik, P.V.; Yogeeswari, P.; Sriram, D.A series of pyridazino[4,5-b]indole derivatives containing alkyl-, benzyl- and phenacyl-substituted 1,2,3-triazolylmethyl units was synthesized using click chemistry approach. All 30 compounds of the series were screened in vitro against four cancer cell lines, viz. breast cancer cells MDA-MB-231 and MCF 7, human primary glioblastoma U-87 and human neuroblastoma IMR-32 cell lines. Most of the compounds exhibited potent cancer cell growth inhibition activity at very low micromolar concentrations. The IC50 value of compounds 7v and 7x against human neuroblastoma IMR-32 cell line is 0.07 and 0.04 ?M, respectively. Among the tested compounds, ten compounds showed IC50 value less than 1 ?M against MDA-MB-231 cells, whereas against IMR-32 cells, nine compounds and, against U-87 cells, six compounds showed similar inhibition activity. Further, these molecules exhibited prominent binding affinity and docking scores in the molecular simulation study with the target enzyme PI3 kinase. Graphical Abstract: This paper illustrates the synthesis of new fused indole-pyridazinone derivatives containing substituted 1,2,3-triazoles via click chemistry approach. Most of the compounds exhibited potent cancer cell growth inhibition activity at very low micromolar concentrations. [Figure not available: see fulltext.] © 2015 Springer Science+Business Media New York.Item Novel Indole-Quinazolinone Based Amides as Cytotoxic Agents(HeteroCorporation support@jhetchem.com, 2016) Gokhale, N.; Panathur, N.; Udayakumar, D.; Nayak, P.G.; Pai, K.S.R.Indole-quinazolinone hybrids with active amides were synthesized, characterized, and assessed for their cytotoxicity. Two molecules displayed substantial activity in sulphorhodamine B assay method. © 2015 HeteroCorporation.Item Design and: In vitro biological evaluation of substituted chalcones synthesized from nitrogen mustards as potent microtubule targeted anticancer agents(Royal Society of Chemistry, 2017) Sabina, X.J.; Karthikeyan, J.; Velmurugan, G.; Muthu Tamizh, M.M.; Nityananda Shetty, A.N.A new series of p-[N,N-bis(2-chloroethyl)amino]benzaldehyde substituted chalcone derivatives were designed and synthesized, and their structures were characterized by spectroscopic techniques and single crystal XRD studies. Compounds 3a-f crystallized in the triclinic system with a centrosymmetric space group P1, except for crystal 3c which crystallized in the monoclinic crystal system with a centrosymmetric space group P21/c. Molecular docking studies were utilized to reveal the binding mode of the derivatives to identify new tubulin inhibitors. Density functional theory calculations were performed to understand the structural and electronic properties of these chalcones. The DFT results show that the HOMOs of all the chalcones lie in the range of -5.65 to -6.17 eV and the LUMOs in the range of -2.01 to -3.21 eV. The experimental results are well supported by the theoretical structural analysis. The biological activity of these compounds showed high potency of growth inhibitory effects with sub-micromolar IC50 values ranging from 0.089 to 0.200 ?M against A549 and HepG2 cancer cell lines. Furthermore, these compounds exhibited a strong inhibitory effect on tubulin polymerization. 3e showed the highest mean activity against both the cancer cells and in tubulin inhibition. This correlated well with the theoretical results from the pharmacophore binding model. Hence, these six compounds, particularly 3e, could be considered as potential leads in the development of new anticancer agents. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2017.Item Nisin gold nanoparticles assemble as potent antimicrobial agent against Enterococcus faecalis and Staphylococcus aureus clinical isolates(Editions de Sante editions.de.sante@wanadoo.fr, 2017) Pradeepa, n.; Bhat, K.U.; Vidya, S.M.Enterococci and staphylococci have the potency to acquire resistant to antibiotics and have emerged as serious nosocomial pathogens responsible for various diseases. The continuous seeking of new antimicrobials against these pathogens is the only way to avoid the rapid spreading of diseases. Controlled fabrication of existing antimicrobials with nanoparticles offers an alternative strategy to combat against these pathogens with an effective manner. In the present study, gold nanoparticles (AuNPs) were functionalized with nisin to kill a wide range of clinically isolated Enterococcus faecalis and Staphylococcus aureus strains. Nisin functionalized gold nanoparticles (NAuNPs) exhibited good inhibitory activity against all seven multidrug resistant (MDR) and eight non-MDR E. faecalis and S. aureus strains. Minimum inhibitory concentration of NAuNPs was >8–32 fold lower than nisin. Interestingly, antibiotic resistant was not observed by these pathogens up to 8 generation. TEM and AFM investigation revealed that, the antimicrobial action of NAuNPs appears to act in three sequential stages: membrane destabilization, pore formation, followed by intracellular fluid leakage. In addition, NAuNPs were non toxic and showed less hemolytic activity. These findings indicated that, the NAuNPs can be served as an alternative antimicrobial agent to treat a wide range of enterococcal and staphylococcal infections. © 2016 Elsevier B.V.