Anti-Tubercular Activity of Substituted 7-Methyl and 7-Formylindolizines and In Silico Study for Prospective Molecular Target Identification.
作者： Katharigatta N. Venugopala , Christophe Tratrat , Melendhran Pillay , Fawzi M. Mahomoodally , Subhrajyoti Bhandary
DOI: 10.3390/ANTIBIOTICS8040247
关键词: In vitro 、 Chemistry 、 Rifampicin 、 Mycobacterium tuberculosis 、 In silico 、 DNA 、 Isoniazid 、 Enzyme 、 Molecular biology 、 Minimum inhibitory concentration
摘要: Novel series of diversely substituted indolizines were designed, synthesized, and evaluated for their in vitro anti-mycobacterial activity against H37Rv multi-drug-resistant (MDR) strains Mycobacterium tuberculosis (MTB). Many compounds exhibited significant inhibitory MTB strains. Indolizines 2d, 2e, 4 also found to be active clinical isolates with multi-resistance rifampicin isoniazid. Indolizine was identified as the most promising agent, displaying minimum concentration (MIC) values 32 μg/mL MDR strains, respectively. Furthermore, an silico study carried out prospective molecular target identification revealed favorable interactions enzymes CYP 121, malate synthase, DNA GyrB ATPase. None potent molecules presented toxicity peripheral blood mononuclear (PBM) cell lines, demonstrating potentiality used drug-sensitive drug-resistant therapy.
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sci-hub.se 参考文章(34)
K N, Venugopala, Susanta K Nayak, Melendhran Pillay, Renuka Prasanna, Yacoob M Coovadia, Bharti Odhav, Synthesis and Antitubercular Activity of 2-(substituted phenyl/benzyl-amino)-6-(4-chlorophenyl)-5-(methoxycarbonyl)-4-methyl-3,6-dihydropyrimidin-1-ium Chlorides Chemical Biology & Drug Design. ,vol. 81, pp. 219- 227 ,(2013) , 10.1111/CBDD.12065
KN, Venugopala, Fernando Albericio, Yacoob Mohamed Coovadia, Hendrik G Kruger, Glenn EM Maguire, Melendhran Pillay, Thavendran Govender, Total synthesis of a depsidomycin analogue by convergent solid‐phase peptide synthesis and macrolactonization strategy for antitubercular activity Journal of Peptide Science. ,vol. 17, pp. 683- 689 ,(2011) , 10.1002/PSC.1389
GM Cingolani, F Claudi, M Massi, F Venturi, Indolizine derivatives with biological activity VI 1-(2-aminoethyl)-3-benzyl-7-methoxy-2-methylindolizine, benanserin structural analogue European Journal of Medicinal Chemistry. ,vol. 25, pp. 709- 712 ,(1990) , 10.1016/0223-5234(90)90138-S
Abhijit Hazra, Shyamal Mondal, Arindam Maity, Subhendu Naskar, Pritam Saha, Rupankar Paira, Krishnendu B Sahu, Priyankar Paira, Soma Ghosh, Chandrima Sinha, Amalesh Samanta, Sukdeb Banerjee, Nirup B Mondal, None, Amberlite-IRA-402 (OH) ion exchange resin mediated synthesis of indolizines, pyrrolo [1,2-a] quinolines and isoquinolines: antibacterial and antifungal evaluation of the products. European Journal of Medicinal Chemistry. ,vol. 46, pp. 2132- 2140 ,(2011) , 10.1016/J.EJMECH.2011.02.066
Clifton E Barry, Timing is everything for compassionate use of delamanid Nature Medicine. ,vol. 21, pp. 211- 211 ,(2015) , 10.1038/NM.3823
Edward Cox, Katherine Laessig, FDA Approval of Bedaquiline — The Benefit–Risk Balance for Drug-Resistant Tuberculosis New England Journal of Medicine. ,vol. 371, pp. 689- 691 ,(2014) , 10.1056/NEJMP1314385
P Olejníkova, L Birošová, L Švorc, Antimicrobial and Antimutagenic Properties of Newly Synthesized Derivatives of Indolizine Scientia Pharmaceutica. ,vol. 77, pp. 216- 216 ,(2009) , 10.3797/SCIPHARM.OEPHG.21.PO-17
Stephen C Smith, Eric D Clarke, Stuart M Ridley, David Bartlett, Daren T Greenhow, Harry Glithro, Agnes Y Klong, Glynn Mitchell, Graham W Mullier, Herbicidal indolizine-5,8-diones: photosystem I redox mediators. Pest Management Science. ,vol. 61, pp. 16- 24 ,(2005) , 10.1002/PS.980
Gerd Dannhardt, Wolfgang Meindl, Steffen Gussmann, Samir Ajili, Thomas Kappe, Anti-mycobacterial 7-hydroxy-2,3-dihydro-1H-indolizin-5-ones European Journal of Medicinal Chemistry. ,vol. 22, pp. 505- 510 ,(1987) , 10.1016/0223-5234(87)90290-X
Marcos A. Espinal, The global situation of MDR-TB Tuberculosis. ,vol. 83, pp. 44- 51 ,(2003) , 10.1016/S1472-9792(02)00058-6