Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria

Autor(es):Mostrar menos -

Touitou, Meir ^[1] ; Manetti, Fabrizio ^[2] ; Ribeiro, Camila Maringolo ^[3] ; Pavan, Fernando Rogerio ^[3] ; Scalacci, Nicolo ^[1] ; Zrebna, Katarina ^[1] ; Begum, Neelu ^[4] ; Semenya, Dorothy ^[1] ; Gupta, Antima ^{[5, 6]} ; Bhakta, Sanjib ^[5] ; McHugh, Timothy D. ^[4] ; Senderowitz, Hanoch ^[7] ; Kyriazi, Melina ^[1] ; Castagnolo, Daniele ^[1]

Afiliação do(s) autor(es)

^[1] Kings Coll London, Sch Canc & Pharmaceut Sci, 150 Stamford St, London SE1 9NH - England

^[2] Dipartimento Biotecnol Chim & Farm, Via A Moro 2, I-53100 Siena - Italy

^[3] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, TB Res Lab, Rod Araraquara Jau, Km1, BR-14800903 Araraquara, SP - Brazil

^[4] UCL, Ctr Clin Microbiol, London NW3 2PF - England

^[5] Birkbeck Univ London, Inst Struct & Mol Biol, Dept Biol Sci, Mycobacteria Res Lab, Malet St, London WC1E 7HX - England

^[6] London Sch Hyg & Trop Med, Fac Infect Dis, London WC1E 7HT - England

^[7] Bar Ilan Univ, Fac Exact Sci, Dept Chem, IL-5290002 Ramat Gan - Israel

• Tipo de documento: Artigo Científico
• Fonte: ACS Medicinal Chemistry Letters; v. 11, n. 5, p. 638-644, MAY 14 2020.
• Citações Web of Science: 0

Resumo

A series of N-phenyl-2,5-dimethylpyrrole derivatives, designed as hybrids of the antitubercular agents BM212 and SQ109, have been synthesized and evaluated against susceptible and drug-resistant mycobacteria strains. Compound 5d, bearing a cyclohexylmethylene side chain, showed high potency against M. tuberculosis including MDR-TB strains at submicromolar concentrations. The new compound shows bacteriostatic activity and low toxicity and proved to be effective against intracellular mycobacteria too, showing an activity profile similar to isoniazid. (AU)

• Processo FAPESP: 18/00163-0 - Desenvolvimento e busca de novos antimicrobianos contra Tuberculose: da triagem a estudos pré-clínicos in vivo
• Beneficiário: Fernando Rogério Pavan
• Modalidade de apoio: Auxílio à Pesquisa - Regular