Synthesis, molecular modeling and preliminary biological evaluation of a set of 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazole as potential antibacterial, anti-Trypanosoma cruzi and antifungal agents

• Published in: Bioorganic & medicinal chemistry 2011-11, Vol.19 (21), p.6292-6301
• Main Authors: Ishii, Marina, Jorge, Salomão Dória, de Oliveira, Alex Alfredo, Palace-Berl, Fanny, Sonehara, Ieda Yuriko, Pasqualoto, Kerly Fernanda Mesquita, Tavares, Leoberto Costa
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antiparasitic agents; Antiprotozoal Agents - chemical synthesis; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Bacterial resistance; Biological and medical sciences; Candida albicans; Candida albicans - drug effects; Data processing; General aspects; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; Medical sciences; Microbial Sensitivity Tests; Microorganisms; Minimum inhibitory concentration; Models, Molecular; Molecular Dynamics Simulation; Molecular modelling; MRSA; Oxadiazoles - chemical synthesis; Oxadiazoles - chemistry; Oxadiazoles - pharmacology; Oxadiazolines; Parasites; Pharmacology. Drug treatments; Physicochemical properties; Population growth; Staphylococcus aureus; Staphylococcus aureus - drug effects; Structure-Activity Relationship; Trypanosoma cruzi; Trypanosoma cruzi - drug effects; VISA
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2011.09.009

A novel set of 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazole has been synthesized and its antiprotozoal, antibacterial and antifungal activities evaluated. Also, their physicochemical and structural properties were explored to establish qualitative property-activity relationships. A series of 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazole derivatives was synthesized and their activity screened in vitro against Staphylococcus aureus, Trypanosoma cruzi, and Candida albicans. The bioactivity was expressed as minimum inhibitory concentration (MIC) for S. aureus strains, and as fifty-percent inhibitory concentration (IC50) of parasite population growth for T. cruzi. A molecular modeling approach was performed to establish qualitative relationships regarding the biological data and the compounds’ physicochemical properties. The 5-(4-OC4H9Ph, 5l), and 5-(4-CO2CH3Ph, 5o) derivatives were the most active compounds for S. aureus ATCC 25923 (MIC=1.95–1.25μg/mL) and T. cruzi (IC50=7.91μM), respectively. Also, a preliminary evaluation against C. albicans involving some compounds was performed and the 5-(4-CH3Ph, 5e) derivative was the most active compound (MIC=3.28–2.95μg/mL). In this preliminary study, all synthesized 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazole derivatives were active against all microorganisms tested.