02320nas a2200193   4500008004100000022001400041245013500055210006900190260000800259300001600267490000600283520160500289100002301894700002501917700001701942700002001959700001901979856012801998       2018                        eng d  a2046-206900aMolecular modeling studies and in vitro screening of dihydrorugosaflavonoid and its derivatives against mycobacterium tuberculosis0 aMolecular modeling studies and in vitro screening of dihydrorugo  cMAY  a10634-106430 v83 a<p>Novel drug regimens against tuberculosis (TB) are urgently needed and may be developed by targeting essential enzymes of Mtb that sustain the pathogenicity of tuberculosis. In the present investigation, series of compounds (5a-f and 6a-f) based on a naturally occurring rugosaflavonoid moiety were evaluated by in silico molecular modeling studies against -ketoacyl-ACP reductase (MabA) (PDB ID: IUZN) and pantothenate kinase (PanK) (PDB ID: ; 3AF3). Compounds 5a, 5c, 5d, and 6c, which had docking scores of -8.29, -8.36, -8.17 and -7.39 kcal mol(-1), respectively, displayed interactions with MabA that were better than those of isoniazid (-6.81 kcal mol(-1)). Similarly, compounds 5a, 5c, 5d, and 6c, which had docking scores of -7.55, -7.64, -7.40 and -6.7 kcal mol(-1), respectively, displayed interactions with PanK that were comparable to those of isoniazid (-7.64 kcal mol(-1)). Because of their docking scores, these compounds were screened in vitro against Mycobacterium tuberculosis H37Ra (Mtb) using an XRMA protocol. Among the screened compounds, the dihydrorugosaflavonoid derivatives 5a, 5c, and 5d had IC50 values of 12.93, 8.43 and 11.3 g mL(-1), respectively, and exhibited better inhibitory activity than the parent rugosaflavonoid derivatives. The rugosaflavonoid derivative 6c had an IC50 value of 17.57 g mL(-1). The synthesized compounds also displayed inhibitory activity against the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus. The present study will be helpful for the further development of these molecules into antitubercular lead candidates.</p>1 aPuranik, Ninad, V.1 aSrivastava, Pratibha1 aSwami, Sagar1 aChoudhari, Amit1 aSarkar, Dhiman  uhttp://library.ncl.res.in/content/molecular-modeling-studies-and-vitro-screening-dihydrorugosaflavonoid-and-its-derivatives02138nas a2200289   4500008004100000022001400041245018100055210006900236260000800305300001400313490000700327520111900334653001501453653003101468653001201499653001901511653001101530653003101541100002301572700001701595700002301612700001801635700002701653700001901680700002501699856012401724       2022                        eng d  a1478-641900aFirst synthesis of podocarflavone A and its analogs and evaluation of their antimycobacterial potential against mycobacterium tuberculosis with the support of virtual screening0 aFirst synthesis of podocarflavone A and its analogs and evaluati  cAUG  a3879-38860 v363 a<p>
	The first synthetic route developed for Podocarflavone A reported from Podocarpus macrophyllus and its analogs in 7 steps. Computational analysis for binding with the pantothenate kinase (3AVO) of Mycobacterium tuberculosis showed their docking score (ds) in the range of -8.9 to -9.3 Kcal/mol. MD simulations delineated the stability of the protein-ligand complexes in the TIP3P model. MMGBSA and MMPBSA values of 8d were -42.46 Kcal/mol and -14.58 Kcal/mol, respectively. Further in-vitro antitubercular screening of compounds 8a, 8d, and 8e against M. tuberculosis H37Ra using XRMA protocol exhibited promising antimycobacterial activity with IC50 values 21.82 mu g/mL, 15.55 mu g/mL, and 16.56 mu g/mL, respectively. Compounds 8a, 8d, and 8e showed antibacterial activity with IC50 values 41.56 mu g/mL, 24.72 mu g/mL, and 72.45 mu g/mL respectively against the Staphylococcus aureus. 8a and 8d showed inhibition with IC50 values 39.6 mu g/mL and 27.64 mu g/mL, respectively, against Bacillus subtilis. The present study could help in the further development of lead molecules against tuberculosis.</p>
10aand MMGBSA10aantimycobacterial activity10adocking10aMD simulations10aMMPBSA10aPodocarflavone A synthesis1 aPuranik, Ninad, V.1 aSwami, Sagar1 aMisar, Ashwini, V.1 aMamgain, Ritu1 aGulawani, Swapnaja, S.1 aDhiman, Sarkar1 aSrivastava, Pratibha  uhttp://library.ncl.res.in/content/first-synthesis-podocarflavone-and-its-analogs-and-evaluation-their-antimycobacterial