Synthesis, molecular modeling studies and evaluation of antifungal activity of a novel series of thiazole derivatives

• Published in: European journal of medicinal chemistry Vol. 151; pp. 248 - 260
• Main Authors: Lino, Cleudiomar Inácio, Gonçalves de Souza, Igor, Borelli, Beatriz Martins, Silvério Matos, Thelma Tirone, Santos Teixeira, Iasmin Natália, Ramos, Jonas Pereira, Maria de Souza Fagundes, Elaine, de Oliveira Fernandes, Philipe, Maltarollo, Vinícius Gonçalves, Johann, Susana, de Oliveira, Renata Barbosa
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 10.05.2018; Elsevier
• Subjects: Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Candida - drug effects; Candidiasis - drug therapy; Chemistry, Medicinal; Cryptococcosis - drug therapy; Cryptococcus - drug effects; HEK293 Cells; Humans; Hydrazine-thiazoles; Life Sciences & Biomedicine; Microbial Sensitivity Tests; Models, Molecular; Paracoccidioides - drug effects; Paracoccidioidomycosis - drug therapy; Pharmacology & Pharmacy; QSAR; Science & Technology; Structure-Activity Relationship; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology; QSAR; Hydrazine-thiazoles; Antifungal agents; MANAGEMENT; SEMICARBAZONES; DOCKING; ALBICANS; ANTIMICROBIAL ACTIVITY; EPIDEMIOLOGY
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2018.03.083

In the search for new antifungal agents, a novel series of fifteen hydrazine-thiazole derivatives was synthesized and assayed in vitro against six clinically important Candida and Cryptococcus species and Paracoccidioides brasiliensis. Eight compounds showed promising antifungal activity with minimum inhibitory concentration (MIC) values ranging from 0.45 to 31.2 μM, some of them being equally or more active than the drug fluconazole and amphotericin B. Active compounds were additionally tested for toxicity against human embryonic kidney (HEK-293) cells and none of them exhibited significant cytotoxicity, indicating high selectivity. Molecular modeling studies results corroborated experimental SAR results, suggesting their use in the design of new antifungal agents. [Display omitted] •Fifteen hydrazine-thiazole derivatives were synthesized.•The compounds were evaluated against clinically important Candida and Cryptococcus species.•Eight compounds showed promising antifungal activity (MIC = 0.45–31.2 μM).•Compounds showed remarkable selectivity compared to human embryonic kidney (HEK-293) cells.•Molecular modeling studies were also carried out.