@article { ISI:000364803200011, title = {Design and synthesis of a focused library of diamino triazines as potential mycobacterium tuberculosis DHFR inhibitors}, journal = {ACS Medicinal Chemistry Letters}, volume = {6}, number = {11}, year = {2015}, month = {NOV}, pages = {1140-1144}, publisher = {AMER CHEMICAL SOC}, address = {1155 16TH ST, NW, WASHINGTON, DC 20036 USA}, abstract = {

We report design of a series of 2,4-diamino triazines as Mycobacterium tuberculosis (Mtb) dihydrofolate reductase inhibitors. The synthesized compounds were evaluated against Mtb (H(37)Rv and Dormant stage H37Ra), their cytotoxicity was assessed (HepG2 and A549 cell lines), and selectivity toward Mtb was evaluated by testing against other bacterial strains. Some derivatives showed promising activity along with low cytotoxicity. The most potent compound in the whole cell assay (MIC 0.325 mu M against H(37)Rv) showed selectivity in the enzyme assay and exhibited synergy with second line anti-TB agent p-amino salicylic acid. This study therefore provides promising molecules for further development as antituberculosis DHFR inhibitors.

}, keywords = {Diamino triazine, dihydrofolate reductase, enzyme assay, molecular modeling, Mycobacterium tuberculosis, selectivity, synergy}, issn = {1948-5875}, doi = {10.1021/acsmedchemlett.5b00367}, author = {Lele, Arundhati C. and Raju, Archana and Khambete, Mihir P. and Ray, M. K. and Rajan, M. G. R. and Arkile, Manisha A. and Jadhav, Nandadeep J. and Sarkar, Dhiman and Degani, Mariam S.} } @conference {42974, title = {High throughput screening of inhibitors for tuberculosis at NCL : a novel drug discovery initiative from CSIR}, booktitle = {73rd CSIR Foundation Day, at CSIR-National Chemical Laboratory, Pune}, year = {2015}, month = {SEP}, publisher = {CSIR-National Chemical Laboratory, Pune}, organization = {CSIR-National Chemical Laboratory, Pune}, address = {CSIR-National Chemical Laboratory, Pune}, abstract = {

Discover and develop novel drugs that are effective at curing latent, drug sensitive and drug resistant TB Study the biology of tuberculosis bacilli in great detail to identify new metabolic pathways that may be vulnerable to drugs Test thousands of potential drugs in our screening facility to find new compounds or new compound classes that kill TB bacteria Increase throughput up to 20,000 compounds at a time Develop novel screens using conditions that mimic those the TB bacteria encounters in the human body Utilize medical chemistry to optimize the structures of compounds so that they kill TB bacteria in a more potent fashion and are non-toxic Meet the challenges from industry

}, author = {Manek, Hardik and Nawale, Laxman and Jadhav, Nandadeep J. and Sarkar, Dhiman} } @article {45939, title = {Synthesis and evaluation of thieno[2,3-d]pyrimidin-4(3H)-ones as potential antitubercular agents}, journal = {MedChemComm}, volume = {6}, year = {2015}, month = {AUG}, pages = {2209-2215}, type = {Article}, abstract = {

A number of thieno[2,3-d]pyrimidin-4(3H)-ones were designed, synthesized and screened against Mycobacteria as a part of our program to develop new antitubercular agents. It was observed that some of the compounds have significant antimycobacterial activity against Mycobacterium tuberculosis H37Ra (ATCC 25177) and Mycobacterium bovis BCG (ATCC 35743). The active compounds were studied for cytotoxicity against four cell lines and were found to be non-cytotoxic. The results showed that compounds 13b and 29e were found to exhibit very good antimycobacterial activity (MIC in the range of 6-8 mu M) and the thienopyrimidinones as a class have potential to be developed as antitubercular agents.

}, issn = {2040-2503}, doi = {10.1039/c5md00404g}, author = {Borate, Hanumant B. and Annadate, Ritesh A. and Vagh, Sandip S. and Pisal, Mahesh M. and Deokate, Sagar B. and Arkile, Manisha A. and Jadhav, Nandadeep J. and Nawale, Laxman U. and Sarkar, Dhiman} } @article { ISI:000367329700060, title = {Synthesis and bioactivity of novel triazole incorporated benzothiazinone derivatives as antitubercular and antioxidant agent}, journal = {Bioorganic \& Medicinal Chemistry Letters}, volume = {26}, number = {2}, year = {2016}, month = {JAN}, pages = {561-569}, publisher = {PERGAMON-ELSEVIER SCIENCE LTD}, address = {THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND}, abstract = {

In search of new active molecules against Mycobacterium tuberculosis (MTB) H37Ra and M. bovis BCG, a small focused library of benzothiazinone based 1,2,3-triazoles has been efficiently prepared via click chemistry approach. Several derivatives were found to be promising inhibitors of MTB and M. bovis BCG characterized by lower MIC values (27.34-29.37 mu g/mL). Among all the synthesized compounds, 6c and 6e is the most active compound against MTB and M. bovis BCG. The compounds were further tested for anti-proliferative activity against HeLa, A549 and A431 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Further, the synthesized compounds were found to have potential antioxidant activity with IC50 range = 14.14-47.11 mu g/mL. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against a potential target MTB DprE1, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of the in vitro and in silico study suggest that the triazole incorporated benzothiazinone may possess the ideal structural requirements for further development of novel therapeutic agents. (C) 2015 Elsevier Ltd. All rights reserved.

}, keywords = {1, 2, 3-Triazole, ADME prediction, Antioxidant, Antitubercular, Docking study}, issn = {0960-894X}, doi = {10.1016/j.bmcl.2015.11.071}, author = {Shaikh, Mubarak H. and Subhedar, Dnyaneshwar D. and Arkile, Manisha A. and Khedkar, Vijay M. and Jadhav, Nandadeep J. and Sarkar, Dhiman and Shingate, Bapurao B.} } @article { ISI:000370693900022, title = {Synthesis and evaluation of thieno[2,3-d]pyrimidin-4(3H)-ones as potential antitubercular agents (vol 6, pg 2209, 2015)}, journal = {Medchemcomm}, volume = {7}, number = {2}, year = {2016}, month = {DEC}, pages = {379}, publisher = {ROYAL SOC CHEMISTRY}, address = {THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND}, issn = {2040-2503}, doi = {10.1039/c5md90062j}, author = {Borate, Hanumant B. and Annadate, Ritesh A. and Vagh, Sandip S. and Pisal, Mahesh M. and Deokate, Sagar B. and Arkile, Manisha A. and Jadhav, Nandadeep J. and Nawale, Laxman U. and Sarkar, Dhiman} }