title: Recent progress in the drug development of coumarin derivatives as potent antituberculosis agents.
abstract: Tuberculosis (TB) is still a challenging worldwide health problem and mycobacterium tuberculosis (MTB) remains one of the most deadly human pathogens. TB is the second leading infectious cause of mortality today behind only HIV/AIDS. The impetus for developing new structural classes of antituberculosis drugs comes from the emergence of multi-drug resistant (MDR) strains. The development of MDR strains to commonly used drugs is due to, longer durations of therapy as results of resistance, and the resurgence of the disease in immune compromised patients. Therefore, there is an urgent need to explore new antitubercular (anti-TB) agents. Ironically, the low number of potentially new chemical entities which can act as anti-TB candidates is of great importance at present situation. Considering the severity of the problem, WHO has prepared a strategic plan in Berlin declaration 2007 to stop TB, globally. Among the oxygen heterocycles, coumarin derivatives are important motifs, which can be widely found in many natural products, and many of them displaying diverse biological activities. This spectacular spectrum of applications has intrigued organic and medicinal chemists for decades to explore the natural coumarins or their synthetic analogs for their applicability as anti-TB drugs. To pave the way for the future research, there is a need to collect the latest information in this promising area. In the present review, we collated published reports on coumarin derivatives to shed light on the insights on different types of methods reported for their preparations, characterizations and anti-TB applications, so that its full therapeutic potential class of compounds can be utilized for the treatment of tuberculosis. Therefore, the objective of this review is to focus on important coumarin analogs with anti-TB activities, and structure-activity relationships (SAR) for designing the better anti-TB agents. It is hoped that, this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic coumarin-based anti-TB drugs.
authors.affiliation: Centre for Nano and Material Sciences, Jain University, Jain Global Campus, Bangalore, 562112 Karnataka, India. Electronic address: keriphd@gmail.com.
authors.forename: Rangappa S
authors.initials: RS
authors.lastname: Keri
authors.affiliation: Organic Chemistry Section, National Institute for Interdisciplinary Science and Technology (CSIR), Trivandrum 695019, India.
authors.forename: B S
authors.initials: BS
authors.lastname: Sasidhar
authors.affiliation: Centre for Nano and Material Sciences, Jain University, Jain Global Campus, Bangalore, 562112 Karnataka, India.
authors.forename: Bhari Mallanna
authors.initials: BM
authors.lastname: Nagaraja
authors.affiliation: Centro de Quimica Estrutural, Instituto Superior Técnico, Universidade Técnica de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal.
authors.forename: M Amélia
authors.initials: MA
authors.lastname: Santos
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D003374:Coumarins
keywords: Antitubercular; Coumarin; Mycobacterium tuberculosis; Synthesis; Tubercle bacillus