An article Novel pyrazine based anti-tubercular agents: Design, synthesis, biological evaluation and in silico studies WOS:000516796900043 published article about MYCOBACTERIUM-TUBERCULOSIS; ANTIMYCOBACTERIAL ACTIVITY; ACID HYDRAZONES; DERIVATIVES; RESISTANCE; DOCKING; DRUGS; GRANULOCYTES; INHIBITORS; PREDICTION in [Hassan, Nayera W.; Saudi, Manal N.; Abdel-Ghany, Yasser S.; Ismail, Azza; Elzahhar, Perihan A.; El-Hawash, Soad A.] Alexandria Univ, Fac Pharm, Dept Pharmaceut Chem, Alexandria 21521, Egypt; [Sriram, Dharmarajan] Birla Inst Technol & Sci Pilani, Med Chem & Drug Discovery Res Lab, Pharm Grp, Hyderabad Campus, Jawahar Nagar 500078, Telangana, India; [Nassra, Rasha] Alexandria Univ, Fac Med, Dept Med Biochem, Alexandria, Egypt; [Abdel-Aziz, Marwa M.] Al Azhar Univ, Reg Ctr Mycol & Biotechnol, Cairo 11759, Egypt in 2020, Cited 84. Name: Pyrazine-2-carboxylic acid. The Name is Pyrazine-2-carboxylic acid. Through research, I have a further understanding and discovery of 98-97-5
TB continues to be a leading health threat despite the availability of powerful anti-TB drugs. We report herein the design and synthesis of various hybrid molecules comprising pyrazine scaffold and various formerly identified anti-mycobacterial moieties. Thirty-one compounds were screened in vitro for their activity against Mycobacterium tuberculosis H37Rv strain using MABA assay. The results revealed that six compounds (8a, 8b, 8c, 8d, 14b and 18) displayed significant activity against Mtb with MIC values <= 6.25 mu g/ml versus 6.25 mu g/ml for pyrazinamide. The most active compounds were then assessed for their in vitro cytotoxicity against PBMC normal cell line using MTT assay and showed SI > 200. Several in silico studies have been carried out for target fishing of the novel compounds such as shape-based similarity, pharmacophore mapping and inverse docking. Based on this multi-step target fishing study, we suggest that pantothenate synthetase could be the possible target responsible for the action of these compounds. The most active compounds were then successfully docked into the active site of pantothenate synthetase enzyme with favorable binding interactions. In addition, in silico prediction of physicochemical, ADMET and drug-like properties were also determined indicating that compounds 8b, 8c and 8d are promising candidates for the development of new anti-TB agents with enhanced activity and better safety profile.
Name: Pyrazine-2-carboxylic acid. About Pyrazine-2-carboxylic acid, If you have any questions, you can contact Hassan, NW; Saudi, MN; Abdel-Ghany, YS; Ismail, A; Elzahhar, PA; Sriram, D; Nassra, R; Abdel-Aziz, MM; El-Hawash, SA or concate me.
Reference:
Patent; Chevron Research Company; US4732894; (1988); A;,
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