02091nas a2200241   4500008004100000022001400041245016100055210006900216260000900285300001500294490000600309520119300315653002901508653002601537653001901563653003701582653001901619100001801638700001701656700001901673700002501692856013201717       2023                        eng d  a2365-654900aDesign, synthesis, and in vitro biological evaluation of ROS-generating phenanthridin-trione-epoxide conjugates as agents against mycobacterium tuberculosis0 aDesign synthesis and in vitro biological evaluation of ROSgenera  cJUL   ae2023004160 v83 a<p>
	Tuberculosis (TB) is one of the devasting infectious diseases and continues to spread among people despite having several specific drugs. Total eradication of TB is one of the shared interests of both the World Health Organization (WHO) and India globally. A library of antitubercular 6-((1-(aryl/heteroaryl)-1H-1,2,3-triazol-4-yl)methyl)oxireno[2,3-b] phenanthridine-5,7,9(6H,7aH,8aH)-trione (6 a-e) has been prepared in five steps including click chemistry and tested against active and dormant strains of Mycobacterium tuberculosis H37Ra using XRMA protocol. The result showed the inhibitory potential of 6 d IC50 at 0.74 &amp; mu;g/mL concentration against active strain and at 0.9 &amp; mu;g/mL against the dormant strain of Mtb. ROS generating ability of the compounds has been confirmed by luminol, H2O2, and glutathione assays. The molecular docking with the thioredoxin protein of Mtb showed a docking score of -9.6 Kcal/mol. To understand the mechanism with the thioredoxin protein of Mtb, the adduct formation of compounds with cystine was confirmed with HPLC. The involvement of lead molecules with existing drugs can be helpful in the eradication of tuberculosis.</p>
10aantimycobacterial agents10aComputational docking10aCystine adduct10aEpoxy-Phenanthridinone-triazoles10aROS generation1 aMamgain, Ritu1 aSwami, Sagar1 aSarkar, Dhiman1 aSrivastava, Pratibha  uhttps://library.ncl.res.in/content/design-synthesis-and-vitro-biological-evaluation-ros-generating-phenanthridin-trione-epoxide