01879nas a2200325   4500008004100000022001400041245012300055210006900178260007100247300001400318490000600332520075200338653002101090653002801111653001701139653002301156653003101179653001601210653001201226100002401238700001801262700002401280700001601304700002101320700002401341700002601365700001901391700002301410856012001433       2015                        eng d  a1948-587500aDesign and synthesis of a focused library of diamino triazines as potential mycobacterium tuberculosis DHFR inhibitors0 aDesign and synthesis of a focused library of diamino triazines a  a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcNOV  a1140-11440 v63 a<p>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.</p>10aDiamino triazine10adihydrofolate reductase10aenzyme assay10amolecular modeling10aMycobacterium tuberculosis10aselectivity10asynergy1 aLele, Arundhati, C.1 aRaju, Archana1 aKhambete, Mihir, P.1 aRay, M., K.1 aRajan, M., G. R.1 aArkile, Manisha, A.1 aJadhav, Nandadeep, J.1 aSarkar, Dhiman1 aDegani, Mariam, S.  uhttps://library.ncl.res.in/content/design-and-synthesis-focused-library-diamino-triazines-potential-mycobacterium-001943nas a2200253   4500008004100000022001400041245012700055210006900182260007600251300001200327490000600339520101400345100002301359700001501382700001801397700002401415700002001439700002201459700002101481700002301502700001901525700002301544856012201567       2015                        eng d  a1756-891900aRational drug design, synthesis and biological evaluation of dihydrofolate reductase inhibitors as antituberculosis agents0 aRational drug design synthesis and biological evaluation of dihy  aUNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLANDbFUTURE SCI LTDcJUN  a979-9880 v73 a<p>Background: A series of 2,4-diamino-s-triazines was designed, with potential for activity against Mycobacterium tuberculosis (Mtb) dihydrofolate reductase enzyme, on the basis of virtual screening results and structure-based drug design. Results: The compounds were evaluated against Mtb (H(37)Rv) and their cytotoxicity was assessed using VERO cell lines. Of particular note, two compounds were found to have the most promising antituberculosis activity (6b minimum inhibitory concentration: 1.76 mu M and 6i minimum inhibitory concentration: 1.57 mu M) along with low cytotoxicity (CC50 : &gt; 300 mu M). The enzyme assay results of these two indicated significant inhibition of Mtb dihydrofolate reductase along with selectivity. Selected derivatives were tested against dormant tubercle bacilli in vivo and ex vivo indicating potential inhibition. Conclusion: This study provides promising antituberculosis dihydrofolate reductase inhibitors that can act as potential leads for further development.</p>1 aTawari, Nilesh, R.1 aBag, Seema1 aRaju, Archana1 aLele, Arundhati, C.1 aBairwa, Ranjeet1 aRay, Mukti, Kanta1 aRajan, M., G. R.1 aNawale, Laxman, U.1 aSarkar, Dhiman1 aDegani, Mariam, S.  uhttps://library.ncl.res.in/content/rational-drug-design-synthesis-and-biological-evaluation-dihydrofolate-reductase-001495nas a2200229   4500008004100000022001400041245007200055210006900127260000800196300001400204490000700218520075800225100002200983700002301005700002301028700002101051700002401072700001901096700002601115700002401141856010001165       2018                        eng d  a1756-891900a Rational design of coumarin derivatives as antituberculosis agents0 aRational design of coumarin derivatives as antituberculosis agen  cOCT  a2431-24440 v103 aA series of coumarin derivatives was designed as potential antituberculosis agents. Results: The compounds were screened against active and dormant Mycobacterium tuberculosis (Mtb). Compounds 3k and 3n were found to have the most promising activity against replicating MtbH37Rv exhibiting minimum inhibitory concentration of 4.63 and 9.75 mu M respectively. The compounds were also effective against dormant MtbH37Rv exhibiting more potency than the standard drugs, isoniazid and rifampicin. The compounds were found to be non-cytotoxic against human cell lines. Conclusion: This study provides promising antituberculosis agents that are effective against replicating as well as dormant Mtb and can thus act as potential leads for further development.
1 aMali, Hemlata, M.1 aSabale, Sandip, S.1 aDegani, Mariam, S.1 aBorkute, Rachana1 aChoudhari, Amit, S.1 aSarkar, Dhiman1 aKrishna, Vagolu, Siva1 aSriram, Dharmarajan  uhttps://library.ncl.res.in/content/rational-design-coumarin-derivatives-antituberculosis-agents