Synthesis and biological evaluation of new 13-n-nonylprotoberberine derivatives as antitubercular agents

Tuberculosis is a serious threat to public health throughout the world. A series of new 13-n-nonylprotoberberine derivatives was designed, synthesized and evaluated for anti-mycobacterial activity against Mycobacterium tuberculosis strain H(37)Rv. Several compounds (2, 11a-c, 11g, 13d, 15c) exhibited excellent anti-tubercular activity with an MIC below 1.0 mu g/mL. Notably, compound 13d showed potential antibacterial effect against both drug-susceptible and multidrug-resistant (MDR) M. tuberculosis with MIC ranges of 0.0625-1.0 mu g/mL. These results suggest a mode of action different from that of the current anti-mycobacterial drugs rifampicin and isoniazid. Hence, compound 13d is an attractive lead compound for the development of new antitubercular agents. (C) 2013 Institute of Materia Medica, Chinese Academy of Medical Sciences and Chinese Pharmaceutical Association. Production and hosting by Elsevier B.V. All rights reserved.