Leubethanol antimicobacterial activity improvement

Abstract

The tuberculosis mainly caused by Mycobacterium tuberculosis (MTB) remains a worldwide major health problem. It represents the greatest killer worldwide due to a single infectious agent. According to the latest WHO report [1], in 2012, 8.6 million people fell ill with TB and 1.3 million died from TB. Over 95% of TB deaths occur in low- and middle-income countries, and it is among the top three causes of death for women aged 15 to 44. The use of established drugs like isoniazid, rifampicin and ethambutol (EMB), very useful and effective in the past, are ineffective against multiresistant strains (MRS-TB) and the co-infection TB-AIDS in addition to other causes, has promoted the emergence of resistant strains extremely (XDR-TB) [2]. These circumstances make necessary the development of new and more effective drugs. Research groups of the University of Salamanca (Spain) and of the Autonomous University of Nuevo Leon (Mexico), “Pharmaceutical Chemistry” and “Analytical Chemistry”, respectivily, have been working in recent years in the research and development of new molecules effective against MTB that could prevent the growth of normal and multi-drug resistant strains. Therefore, starting from natural [3] and synthetic (EMB) [4] models have obtained substances with more potent and selective anti-MTB activity. Based on the structure of the natural diterpene leubethanol chemical transformations to improve its antimycobacterial activity have been made. Leubethanol was conveniently isolated, purify and characterized from Leucophyllum frutescens root bark. Modifications on the aromatic ring (electron withdrawing groups), on the aliphatic chain (CHO, COOH, C = NOH, heterocycles) and also dimeric compounds were obtained. All the compounds were evaluated against H37Rv and MDR strains of MTB, some of them exceeded Leubetanol activity.