title: Recycling and refurbishing old antitubercular drugs: the encouraging case of inhibitors of mycolic acid biosynthesis.
abstract: One of the first approaches undertaken in the quest for antitubercular compounds was that of understanding the mechanism of action of old drugs and proposing chemical modifications or other strategies to improve their activity, generally lost to the mechanisms of resistance developed by Mycobacterium tuberculosis. A leading case was the work carried out on a set of compounds with proven activity on the essential pathway of the synthesis of mycolic acids. As a result, different solutions were presented, improving the activity of those inhibitors or producing novel compounds acting on the same molecular target(s), but avoiding the most common resistance strategies developed by the tubercle bacilli. This review focuses on the activity of those compounds, developed following the completion of the studies on several of the classic antitubercular drugs.
authors.affiliation: Cátedra de Microbiología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100 (2000), Rosario, Argentina.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Belardinelli
authors.forename: Héctor R
authors.initials: HR
authors.lastname: Morbidoni
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D005000:Ethionamide / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007538:Isoniazid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000378:metabolism; D009171:Mycolic Acids / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010670:Phenylthiourea / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013828:Thioacetazone / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D009171:Mycolic Acids; C100189:thiocarlide; D010670:Phenylthiourea; D013828:Thioacetazone; D005000:Ethionamide; D007538:Isoniazid