Mouse Anti-M. tuberculosis 16kDa Monoclonal antibody, clone 6287

Mycobacterium tuberculosis (MTB) infection has become a growing health risk as multi-drug resistant strain (MDR-MTB) has emerged worldwide. The development of isoniazid (INH)-resistant M. tuberculosis strains dictate the need to re-design this old drug to create effective analogs against the resistant INH strains. Synthesis and the biological activity of isoniazid and pyridine derivatives were successfully carried out with elaborated characterization by spectral data. Amongst the synthesized compounds; 1 and 2 displayed encouraging antimycobacterial activity with IC50 of 3.2 mu M and 1.5 mu M against the H37Rv strain. The MIC of test compounds 1 and 2 were also assessed against the 5 drug resistant isolates (FQ-R1, INH-R1, INH-R2, RIF-R1 and RIF-R2) of MTB strains under aerobic conditions and compound 1 [MIC = 3.2 mu M for FQ-R1; MIC = 140 mu M for INH-R1; MIC = 160 mu M for INH-R2; MIC = 2.4 mu M towards RIF-R1; MIC = 4.2 mu M for RIF-R2] and 2 [MIC = 3.3 mu M for FQ-R1; MIC = 170 mu M for INH-R1; MIC= 190 mu M for INH-R2; MIC= 1.8 mu M for RIF-R1; MIC= 8.4 mu M for RIF-R2] have shown significant activity at non-cytotoxic concentration in comparison to the standard drug.

3-(Phenethylamino)demethyl(oxy)aaptamine (1) was re-discovered from the marine sponge of Aaptos sp. as an anti-dormant mycobacterial substance through the bioassay-guided separation. Compound 1 showed potent anti-microbial activity against Mycobacterium bovis BCG with a minimum inhibitory concentration of 0.75 mu g/mL under both aerobic conditions and hypoxic conditions inducing dormant state. Compound 1 was also effective against pathogenic M. tuberculosis strains including clinical multidrug-resistant strains. Furthermore, the successful total syntheses of 1 and its analog 3-aminodemethyl(oxy)aaptamine (2) afford sufficient quantities for further biological studies. (C) 2020 Elsevier Ltd. All rights reserved.