Abstract: A new class of ethylene/propylene-1H-1,2,3-triazole-4-methylene-tethered isatin-coumarin hybrids 8a-j, integrate three anti-tuberculosis pharmacophores coumarin, isatin and 1,2,3-triazole was designed and synthesized. These hybrids were assessed for their in vitro anti-TB activity against MTB H37Rv and MDR-TB, as well as anti-bacterial activity against Gram-positive and Gram-negative strains, and cytotoxicity in VERO cell line. The results showed that all hybrids with acceptable cytotoxicity (CC50: 64-512 μg/mL) exhibited weak to moderate anti-microbial activity. The most active hybrid 8i with MIC of 50 μg/mL against MTB H37Rv and MDR-TB, also has excellent cytotoxicity profile (CC50: 128 μg/mL). The resistance index of hybrid 8i was 1, indicating hybrid 8i has no cross-resistance with the first-line anti-TB agent. Thus, hybrid 8i could act as a lead for further optimization.

Twenty arylsulfonamide derivatives containing 2-arylamino-4(3H)-quinazolinone were synthesized and evaluated for their bioactivities. 4-Fluoro-N-(2-(4-oxo-2-(4-(trifluoromethoxy)phenyl)amino)quinazolin-3(4H)-yl)ethyl benzenesulfonamide, showed excellent activity both against Ralstonia solanacearum and Gibberella zeae with the inhibition rates of 100% (200 mg/L) and 95% (100 mg/L), and 69% (50 mg/L), respectively, exceeding that of the assigned commercial bactericide (thiodiazole-copper) and fungicide (hymexazol). The preliminary structure activity relationships (SAR) showed that both benzene rings of arylamino and arylsulfonamido moieties containing electron-withdrawing substitutes may be preferable for improving the bioactivity of target compounds.