Facile synthesis of benzonitrile/nicotinonitrile based s-triazines as new potential antimycobacterial agents

• A series of benzonitrile/nicotinonitrile and thiazolidin-4-one incorporated s-triazine has been synthesized.
• An efficient Pd-catalyzed C–C Suzuki coupling catalyst system has been developed.
• A series of ligands, palladium sources, bases and solvents were screened to optimize the reaction conditions.
• Synthesized analogs were screened against M. tuberculosis H37Rv.
• Several compounds displayed remarkable antimycobacterial activity in combination with low toxicity towards mammalian cells.

A common strategy to synthesize 4/6-(4-(4-methylpiperazin-1-yl)-6-(4-(4-oxo-2-phenylthiazolidin-3-yl)phenyl)-1,3,5-triazin-2-yloxy)benzonitriles/nicotinonitriles was developed by applying an efficient palladium-catalyzed C–C Suzuki coupling. Moreover, the synthesized compounds were also tested for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv using BACTEC MGIT and Lowenstein–Jensen MIC methods. Several compounds displayed profound antimycobacterial activity in combination with low toxicity towards mammalian cells. The best results were observed amongst the nicotinonitrile substituted s-triazine analogs and it could be a potential starting point to develop new lead compounds in the fight against M. tuberculosis H37Rv. The newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR, MS and elemental analysis.

4/6-(4-(4-methylpiperazin-1-yl)-6-(4-(4-oxo-2-phenylthiazolidin-3-yl)phenyl)-1,3,5-triazin-2-yloxy)benzonitrile/nicotinonitriles were synthesized using Pd-catalyzed C–C coupling and screened in vitro against Mycobacterium tuberculosis H37Rv. Several compounds displayed profound antimycobacterial activity in combination with low toxicity towards mammalian cells.Figure optionsDownload as PowerPoint slide