Faculty Publications

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Publications by NITK Faculty

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    Design and synthesis of some new quinoline-3-carbohydrazone derivatives as potential antimycobacterial agents
    (Elsevier Ltd, 2010) Eswaran, S.; Vasudeva Adhikari, A.V.; Pal, N.K.; Chowdhury, I.H.
    A series of 26 new quinoline derivatives carrying active pharmacophores has been synthesized and evaluated for their in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv (MTB), Mycobacterium smegmatis (MC2), and Mycobacterium fortuitum following the broth micro dilution assay method. Compounds 13e, 13i, 13k, 14a, 14c, 14i, and 14k exhibited significant minimum inhibition concentrations, when compared with first line drugs isoniazid (INH) and rifampicin (RIF) and could be ideally suited for further modifications to obtain more efficacious compounds in the fight against multi-drug resistant tuberculosis. © 2009 Elsevier Ltd. All rights reserved.
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    Design, synthesis and antimicrobial activities of some new quinoline derivatives carrying 1,2,3-triazole moiety
    (2010) Thomas, K.D.; Vasudeva Adhikari, A.V.; Shetty, N.S.
    A new series of [1-(6-methoxy-2-methylquinolin-4-yl)-1H-1,2,3-triazol-4-yl] methanamine derivatives were synthesized starting from 4-methoxyaniline through multi-step reactions. The title compounds 5a-y were prepared by treating the azide intermediate 4 with propargyl bromide and different alkyl/heterocyclic amines in a sequential three component synthesis. All the new compounds were characterized by spectral and elemental analyses. The newly synthesized final compounds were evaluated for their in vitro antibacterial and antifungal activities against pathogenic strains. The preliminary screening results indicated that most of the compounds demonstrated moderate to very good antibacterial and antifungal activities, comparable to the first-line drugs. Twenty five new derivatives of [1-(6-methoxy-2-methylquinolin-4-yl)-1H-1,2,3- triazol-4-yl] methanamine have been synthesized and the most effective compounds have MIC of 6.25 ?g/mL, which are in comparable with present antibiotics. © 2010 Elsevier Masson SAS. All rights reserved.
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    Design, synthesis and docking studies of quinoline-oxazolidinone hybrid molecules and their antitubercular properties
    (2011) Thomas, K.D.; Vasudeva Adhikari, A.V.; Chowdhury, I.H.; Sandeep, T.; Mahmood, R.; Bhattacharya, B.; Sumesh, E.
    New series of quinoline-oxazolidinone hybrid molecules were synthesized based on the preliminary docking studies. All the newly synthesized compounds were characterized by spectral analyses. The newly synthesized compounds were screened for their antimycobacterial properties based on the promising preliminary antibacterial screening results. Amongst tested compounds, compounds 8a, 8j and 13a were active at 0.65 ?g/mL against Mycobacterium tuberculosis H 37Rv strain. The mode of action of these active compounds was carried out by docking of receptor enoyl-ACP reductase with newly synthesized candidate ligands 8a, 8j and 13a. These compounds exhibited well established bonds with one or more amino acids in the receptor active pocket. From the docking studies, compound 8j was considered to be the best inhibitor. © 2011 Elsevier Masson SAS. All rights reserved.
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    Design, synthesis and docking studies of new quinoline-3-carbohydrazide derivatives as antitubercular agents
    (2011) Thomas, K.D.; Vasudeva Adhikari, A.V.; Telkar, S.; Chowdhury, I.H.; Mahmood, R.; Pal, N.K.; Guru Row, T.N.G.; Sumesh, E.
    Three new series of 4-hydroxy-8-trifluoromethyl-quinoline derivatives were synthesized through multi step reactions. All the newly synthesized compounds were characterized by spectral and elemental analyses. The structure of 5j was evidenced by X-ray crystallographic study. The newly synthesized title compounds were evaluated for their antimicrobial activities including antimycobacterial activity. Amongst the tested compounds, 5b, 5e, 5h, 5j, 6c and 7c displayed promising antimicrobial activity. The mode of action of these active compounds was carried out by docking of receptor enoyl-ACP reductase with newly synthesized candidate ligands, 5b, 5e, 5h, 5j and 6c. © 2011 Elsevier Masson SAS. All rights reserved.
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    Design and regioselective synthesis of trifluoromethylquinolone derivatives as potent antimicrobial agents
    (Elsevier Masson SAS infos@masson.fr 62 rue Camille Desmoulins Issy les Moulineaux Cedex 92442, 2013) Garudachari, B.; Isloor, A.M.; Satyanarayana, M.N.; Fun, H.-K.; Pavithra, N.; Kulal, A.
    Three series of new trifluoromethyl substituted quinolone derivatives were synthesized (4a-f, 6a-f and 8a-f) from corresponding substituted anilines by multi-step reactions. The regioselective alkylation with different alkyl halides were carried out by approaching two different routes to get the final products in good yield. Newly synthesized compounds were characterized by spectral study and also by C, H, N analyses. Three dimensional structure of 2b and 4b were also confirmed by single crystal X-ray studies. The final compounds (4a-f, 6a-f and 8a-f) were screened for their in-vitro antibacterial and antifungal activity by well plate method (zone of inhibition). The results revealed that, compounds 4a, 6b, 6c and 8e showed significant antibacterial activity as compared to the standard drug Ciprofloxacin. The compound 8a was found to be a potent antifungal agent. © 2013 Elsevier Masson SAS. All rights reserved.
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    Synthesis, anticonvulsant and anti-inflammatory studies of new 1,4-dihydropyridin-4-yl-phenoxyacetohydrazones
    (Elsevier Masson SAS infos@masson.fr 62 rue Camille Desmoulins Issy les Moulineaux Cedex 92442, 2013) Ulloora, S.; Shabaraya, R.; Ranganathan, R.; Vasudeva Adhikari, A.V.
    The present work involves design and synthesis of new substituted 1,4-dihydropyridin-4-yl-phenoxyacetohydrazones (4a-s, 5a-h), starting from 4-hydroxybenzaldehyde. The final compounds were screened for their in vivo anticonvulsant activity by MES, scPTZ and 6 Hz methods, while their anti-inflammatory screening was performed by Carrageenan induced Paw Edema method. The results indicated that compounds carrying electron donating groups are anticonvulsant active, while most of the tested compounds exhibited significant anti-inflammatory activity. Compounds 4k, l, 4p-s, and 5c showed rapid anti-inflammatory activity within 30 min and appeared as lead compounds. Further, Neurotoxicity study revealed that all the tested compounds are non-toxic up to 300 mg/kg doses. Selected compounds were also subjected to analgesic screening following Tail immersion method and they exhibited good activity. © 2013 Elsevier Masson SAS. All rights reserved.
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    New INH-pyrazole analogs: Design, synthesis and evaluation of antitubercular and antibacterial activity
    (Elsevier Ltd, 2015) Nayak, N.; Ramprasad, J.; Udayakumar, U.
    With the aim of developing promising antitubercular and antibacterial leads, we have designed and synthesized a new series of isonicotinohydrazide based pyrazole derivatives (5a-r). All new derivatives (4a-b and 5a-r) were screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MTB) strain. Four compounds 5j, 5k, 5l and 4b emerged as promising antitubercular agents with MIC of ?4.9 ?M which is much lower than the MIC of the first line antitubercular drug, ethambutol. The 3-chlorophenyl substituent at position-3 of the pyrazole ring enhanced the antiTB activity of the molecules. Three derivatives 5b, 5k and 4b exhibited promising antibacterial activity against the tested bacterial strains. The active molecules were nontoxic to normal Vero cells and showed high selectivity index (>160). The structure and antitubercular activity relationship was further supported by in silico molecular docking study of the active compounds against enoyl acyl carrier protein reductase (InhA) enzyme of M. tuberculosis. © 2015 Published by Elsevier Ltd.
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    Design of new phenothiazine-thiadiazole hybrids via molecular hybridization approach for the development of potent antitubercular agents
    (Elsevier Masson SAS 62 rue Camille Desmoulins Issy les Moulineaux Cedex 92442, 2015) Ramprasad, J.; Nayak, N.; Udayakumar, U.
    A new library of phenothiazine and 1,3,4-thiadiazole hybrid derivatives (5a-u) was designed based on the molecular hybridization approach and the molecules were synthesized in excellent yields using a facile single-step chloro-amine coupling reaction between 2-chloro-1-(10H-phenothiazin-10-yl)ethanones and 2-amino-5-subsituted-1,3,4-thiadiazoles. The compounds were evaluated for their in vitro inhibition activity against Mycobacterium tuberculosis H37Rv (MTB). Compounds 5g and 5n were emerged as the most active compounds of the series with MIC of 0.8 ?g/mL (?1.9 ?M). Also, compounds 5a, 5b, 5c, 5e, 5l and 5m (MIC = 1.6 ?g/mL), and compounds 5j, 5k and 5o (MIC = 3.125 ?g/mL) showed significant inhibition activity. The structure-activity relationship demonstrated that an alkyl (methyl/npropyl) or substituted (4-methyl/4-Cl/4-F) phenyl groups on the 1,3,4-thiadiazole ring enhance the inhibition activity of the compounds. The cytotoxicity study revealed that none of the active molecules are toxic to a normal Vero cell line thus proving the lack of general cellular toxicity. Further, the active molecules were subjected to molecular docking studies with target enzymes InhA and CYP121. © 2015 Elsevier Masson SAS. All rights reserved.
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    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.
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    Design, Synthesis, and Biological Evaluation of New 8-Trifluoromethylquinoline Containing Pyrazole-3-carboxamide Derivatives
    (HeteroCorporation, 2017) Nayak, N.; Ramprasad, J.; Udayakumar, U.
    The article describes the design, synthesis, and characterization of a new series of 8-trifluoromethylquinoline substituted pyrazole-3-carboxamides (9a, 9b, 9c, 9d, 9e, 9f, 9g, 9h, 9i, 9j, 9k, 9l, 9m, 9n, 9o, 9p, 9q, 9r, 9s, 9t) derived from different primary and secondary amines. The intermediate and target compounds were characterized using spectroscopic methods. The structures of intermediate 7 and target molecule 9d were evidenced by the single crystal X-ray study. All the synthesized target compounds (9a, 9b, 9c, 9d, 9e, 9f, 9g, 9h, 9i, 9j, 9k, 9l, 9m, 9n, 9o, 9p, 9q, 9r, 9s, 9t) and three intermediates (6, 7, 8) were screened for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv strain. Two compounds, 9k and 9t, showed significant inhibition activity with MIC of 3.13 µg/mL, which is comparable with the activity of standard drug, ethambutol. The carboxamides derived from benzylamine derivatives were more active than their aniline analogs. In general, the hybrid amides with a N-methylene linkage (-CONHCH2-) exhibited enhanced antitubercular activity. In the antibacterial screening, intermediate 3-hydrazinyl-2-methyl-8-(trifluoromethyl)quinoline (6) displayed remarkable activity against the tested bacterial strains. Further, the active anti-TB derivatives were non-toxic to benign NIH 3T3 cells, which demonstrate the lack of general cellular toxicity and hence signifies their suitability for further lead development. © 2015 HeteroCorporation