title: Developing pyrrole-derived antimycobacterial agents: a rational lead optimization approach.
abstract: Tuberculosis (TB) represents a never-ending challenge toward which research efforts are needed. Drug resistance is the key problem that scientists in the field need to fight. The development of new drugs endowed with novel modes of action against different biological targets is of extreme importance; these new agents should also exhibit lower toxicity compared with the anti-TB drugs currently available. Furthermore, new drugs should be inexpensive since most of the TB-infected population lives in developing nations. In the last few years, numerous researchers have focused their attention on TB, leading to the discovery of some interesting compounds. Among these, the pyrrole-derived compounds we developed can be considered very promising antimycobacterial agents. Aided by molecular modeling studies, we synthesized numerous compounds characterized by the same 1,5-diarylpyrrole scaffold and elucidated very interesting antitubercular/antimycobacterial properties. Some compounds identified are extremely promising and represent a step towards the design of novel lead structures in the fight against TB. Our efforts to this end are reviewed here.
authors.affiliation: Dipartimento di Chimica e Tecnologia del Farmaco, Istituto Pasteur, Fondazione Cenci Bolognetti, Università degli Studi di Roma "La Sapienza", Piazzale A. Moro 5, 00185 Roma, Italy. mariangela.biava@uniroma1.it
authors.forename: Mariangela
authors.initials: M
authors.lastname: Biava
authors.forename: Giulio Cesare
authors.initials: GC
authors.lastname: Porretta
authors.forename: Giovanna
authors.initials: G
authors.lastname: Poce
authors.forename: Claudio
authors.initials: C
authors.lastname: Battilocchio
authors.forename: Salvatore
authors.initials: S
authors.lastname: Alfonso
authors.forename: Alessandro
authors.initials: A
authors.lastname: de Logu
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Manetti
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D014376:Tuberculosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000995:Antitubercular Agents; D011758:Pyrroles