A series of benzamide scaffolds were designed and synthesized by the thiazinone ring opening of PBTZ169, and -benzyl 3,5-dinitrobenzamides were finally identified as anti-TB agents in this work. 3,5-Dinitrobenzamides, ,, and exhibit excellent activity against the drug susceptive H37Rv strain (MIC: 0.0625 μg/mL) and two clinically isolated multidrug-resistant strains (MIC< 0.016-0.125 μg/mL). Compound displays acceptable safety and better pharmacokinetic profiles than PBTZ169, suggesting its promising potential to be a lead compound for future antitubercular drug discovery.

We report herein the design and synthesis of a series of novel Sinefungin (SIN) derivatives, based on the structures of SIN and its analogue EPZ004777. Our results reveal that target compounds 1ad-af, 1ba-bb and 1bf-bh show better activity (IC = 4.56-20.16 μM) than EPZ004777 (IC = 35.19 μM). Surprisingly, SIN was founded to be not as active (IC > 50 μM) as we and other research groups predicted. Interestingly, the intermediates 9a-b and 11b display potent anti-ZIKV potency (IC = 6.33-29.98 μM), and compound 9a also exhibits acceptable cytotoxicity (CC > 200 μM), suggesting their promising potential to be leads for further development.

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We report herein the design and synthesis of a series of novel nitrobenzamide derivatives. Results reveal that A6, A11, C1 and C4 have not only the same excellent MIC values of <0.016 μg/mL against drug-resistant clinical isolates as lead 1, but also acceptable safety indices (SI>1500), opening a new direction for further development.