Synthesis, antimicrobial, and anti-HIV-1 activity of certain 5-(1-adamantyl)-2-substituted thio-1,3,4-oxadiazoles and 5-(1-adamantyl)-3-substituted aminomethyl-1,3,4-oxadiazoline-2-thiones

• Published in: Bioorganic & medicinal chemistry 2004-10, Vol.12 (19), p.5107-5113
• Main Authors: El-Emam, Ali A., Al-Deeb, Omar A., Al-Omar, Mohamed, Lehmann, Jochen
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; General aspects; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; HIV-1 - drug effects; Medical sciences; Microbial Sensitivity Tests; Oxadiazoles - chemical synthesis; Oxadiazoles - pharmacology; Pharmacology. Drug treatments; Structure-Activity Relationship; Thiones - chemical synthesis; Thiones - pharmacology; Virus Replication - drug effects
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2004.07.033

Derivatives of the above structures were synthesized and tested for their in vitro antimicrobial and anti-HIV-1 activity. The reaction of 5-(1-adamantyl)-1,3,4-oxadiazoline-2-thione 2 with iodoethane, 2-dimethylaminoethyl chloride hydrochloride or 2-piperidinoethyl chloride hydrochloride in ethanolic potassium hydroxide yielded the corresponding 5-(1-adamantyl)-2-ethyl or substituted ethylthio-1,3,4-oxadiazoles 3a– c. Interaction of 2 with formaldehyde solution and primary aromatic amines or 1-substituted piperazines, in ethanol at room temperature yielded the corresponding 5-(1-adamantyl)-3-arylaminomethyl-1,3,4-oxadiazoline-2-thiones 4a– m or 5-(1-adamantyl)-3-(4-substituted-1-piperazinylmethyl)-1,3,4-oxadiazoline-2-thiones 5a– h, respectively. All the synthesized compounds were tested for in vitro activities against certain strains of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds 2, 5a, and 5e were found as the most active derivatives, particularly against the Gram-positive bacteria. In addition, the antiviral activity of compounds 2, 4a– m, and 5a– h against HIV-1 using the XTT assay was carried out. Compound 2 produced 100%, 43%, and 37% reduction of viral replication at 50, 10, and 2 μg/mL concentrations, respectively.