Faculty Publications

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    New quinoline derivatives: Synthesis and investigation of antibacterial and antituberculosis properties
    (Elsevier Masson SAS, 2010) Eswaran, S.; Vasudeva Adhikari, A.V.; Chowdhury, I.H.; Pal, N.K.; Thomas, K.D.
    Four new series of quinoline derivatives were synthesized starting from 2-trifluoromethyl aniline through multi-step reactions. In the reaction sequence,substituted aniline was cyclized to 4-hydroxy quinoline 1,which was then transformed to 4-chloro-2,8-bis(trifluoromethyl)quinoline 2. The key scaffold 4-hydrazinyl-2,8-bis(trifluoromethyl)quinoline 3,obtained from the compound 2,was successfully converted to target quinoline derivatives,viz. hydrazones 4aet,ureas 5aee,thioureas 6aec and pyrazoles 7aed,in good yields. The newly synthesized title compounds were evaluated for their in vitro antibacterial activity against Escherichia coli,Staphylococcus aureus,Pseudomonas aeruginosa and Klebsiella pneumoniae (recultured) and antituberculosis activity against Mycobacterium tuberculosis H37Rv and MDR-TB. Preliminary results indicated that most of the hydrazone derivatives demonstrated very good antibacterial and antituberculosis activities while other derivatives showed moderate activity. © 2010 Elsevier Masson SAS. All rights reserved.
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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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    New 1,3-oxazolo[4,5-c]quinoline derivatives: Synthesis and evaluation of antibacterial and antituberculosis properties
    (2010) Eswaran, S.; Vasudeva Adhikari, A.V.; Ajay Kumar, R.
    A new class of fused oxazoloquinoline derivatives was synthesized starting from 2-bromo-1-phenylethanones 1a-b through multi-step reactions. The newly synthesized compounds were evaluated for their in vitro antibacterial against Escherichia coli (ATTC-25922), Staphylococcus aureus (ATTC-25923), Pseudomonas aeruginosa (ATCC-27853) and Klebsiella pneumoniae (recultured) and antituberculosis activity against Mycobacterium tuberculosis H37Rv (ATCC 27294). Preliminary results indicated that most of the compounds demonstrated very good antibacterial and antituberculosis activities which are comparable with the first line drugs. Compounds 6a, 6c, 6g, 6j, 6k and 6n emerged as the lead antitubercular agents with MIC, 1 ?g/mL and 99% bacterial inhibition while eight compounds, viz., 5a, 15k, 6a, 6c, 6g, 6j, 6k and 6n were found to be more potent than INH (MIC: 1.5 ?g/mL) with MIC 1 ?g/mL. © 2009 Elsevier Masson SAS. All rights reserved.
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    New quinolin-4-yl-1,2,3-triazoles carrying amides, sulphonamides and amidopiperazines as potential antitubercular agents
    (2011) Thomas, K.D.; Vasudeva Adhikari, A.V.; Chowdhury, I.H.; Sumesh, E.; Pal, N.K.
    Three new series of quinoline-4-yl-1,2,3-triazoles carrying amides, sulphonamides and amidopiperazines were synthesized through multi-step reactions. The required intermediate, [1-(6-methoxy-2-methylquinolin-4-yl)-1H-1, 2,3-triazol-4-yl]methanol (2) was prepared by treating 4-azido-6-methoxy-2- methylquinoline (1) with propargyl alcohol. Three different series of compounds were synthesized from this intermediate. All the newly synthesized compounds were characterized by spectral and elemental analyses. The structure of 2 was confirmed by X-ray crystallographic study. Further, the title compounds were evaluated for their in vitro anti-bacterial activity against five different bacterial strains and antimycobacterial activity against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis (ATCC 19420) and Mycobacterium fortuitum (ATCC 19542). Title compounds, 6a, 6d, 6i, 6j, 7e, 10a and 10i were found to be active against Mycobacterium tuberculosis H37Rv strain and could be lead molecules of interest. © 2011 Elsevier Masson SAS.
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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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    Synthesis and biological evaluation of new imidazo[2,1-b][1,3,4]thiadiazole-benzimidazole derivatives
    (Elsevier Masson SAS infos@masson.fr 62 rue Camille Desmoulins Issy les Moulineaux Cedex 92442, 2015) Ramprasad, J.; Nayak, N.; Udayakumar, U.; Yogeeswari, P.; Sriram, D.; Peethambar, S.K.; Achur, R.; Santosh Kumar, H.S.S.
    In this report, we describe the synthesis and biological evaluation of a new series of 2-(imidazo[2,1-b][1,3,4]thiadiazol-5-yl)-1H-benzimidazole derivatives (5a-ac). The molecules were analyzed by 1H NMR, 13C NMR, mass spectral and elemental data. The structure of one of the pre-final compounds, 6-(4-methoxyphenyl)-2-(4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde (4d) and that of a target compound, 2-[2-methyl-6-(4-methyl phenyl) imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-1H-benzimidazole (5aa) were confirmed by single crystal XRD studies. All the target compounds were screened for in vitro anti-tuberculosis activity against Mycobacterium tuberculosis H37Rv strain. Seven (5c, 5d, 5l, 5p, 5r, 5z and 5aa) out of twenty nine compounds showed potent anti-tubercular activity with a MIC of 3.125 ?g/mL. A p-substituted phenyl group (p-tolyl or p-chlorophenyl) in the imidazo[2,1-b][1,3,4]thiadiazole ring and/or a chloro group in the benzimidazole ring enhance anti-tuberculosis activity whereas a nitro group in the benzimidazole ring reduces the activity. In the antibacterial screening, compounds 5i, 5w and 5ac showed promising activity against the tested bacterial strains. Further, antifungal and antioxidant activities of these molecules were also investigated. In the cytotoxicity study, the active antitubercular compounds exhibited very low toxicity against a normal cell line. © 2015 Elsevier Masson SAS.
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    One-pot synthesis of new triazole - Imidazo[2,1-b][1,3,4]thiadiazole hybrids via click chemistry and evaluation of their antitubercular activity
    (Elsevier Ltd, 2015) Ramprasad, J.; Nayak, N.; Udayakumar, U.; Yogeeswari, P.; Sriram, D.
    A new series of triazole-imidazo[2,1-b][1,3,4]thiadiazole hybrids (6a-s, 7a) were designed by a molecular hybridisation approach and the target molecules were synthesized via one pot click chemistry protocol. All the intermediates and final molecules were characterised using spectral methods and one of the target compounds (6c) was analysed by the single crystal XRD study. The derivatives were screened for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv strain. Two compounds, 6f and 6n, demonstrated significant growth inhibitory activity against the bacterial strain with a MIC of 3.125 ?g/mL. The presence of chloro substituent on the imidazo[2,1-b][1,3,4]thiadiazole ring and ethyl, benzyl or cyanomethylene groups on the 1,2,3-triazole ring enhance the inhibition activity of the molecules. The active compounds are not toxic to a normal cell line which signifies the lack of general cellular toxicity of these compounds. © 2015 Elsevier Ltd. 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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    Ionic liquid-promoted one-pot synthesis of thiazole-imidazo[2,1-b][1,3,4]thiadiazole hybrids and their antitubercular activity
    (Royal Society of Chemistry, 2016) Ramprasad, J.; Nayak, N.; Udayakumar, D.; Yogeeswari, P.; Sriram, D.
    In this paper, we report the facile and efficient one-pot three-component synthesis of 1-((6-phenylimidazo[2,1-b][1,3,4]thiadiazol-5-yl)methylene)-2-(4-phenylthiazol-2-yl)hydrazine derivatives (5a-w) using an ionic liquid, namely 1-butyl-3-methylimidazolium bromide ([Bmim]Br). The compounds were screened for their in vitro antimycobacterial activity against Mycobacterium tuberculosis. Compound 5s showed the highest inhibitory activity with an MIC of 6.03 ?M which is slightly lower than the MIC values of standard drugs ethambutol (15.3 ?M) and ciprofloxacin (9.4 ?M). Four other compounds of the series viz.5e, 5i, 5t and 5w also showed significant inhibitory activity with MIC values in the range of 11.7-13.9 ?M. The structure-activity relationship revealed that the trifluoromethyl substitution at position-2 and p-chlorophenyl substitution at position-6 of the imidazo[2,1-b][1,3,4]thiadiazole ring enhanced the inhibitory activity. Also, the methyl, methoxy, fluoro or nitro substituents on the thiazole ring enhanced the activity of the compounds. None of the active compounds were toxic to a normal cell line (NIH 3T3), which signifies the lack of general cellular toxicity of the molecules. In silico molecular docking studies revealed the favourable interaction of the potent compounds with the target enzymes InhA and CYP121. © The Royal Society of Chemistry 2016.