A series of novel 1-(4-substitutedbenzoyl)-4-(4-chlorobenzhydryl)piperazine derivatives 5a–g was designed by a nucleophilic substitution reaction of 1-(4-chlorobenzhydryl)piperazine with various benzoyl chlorides and characterized by elemental analyses, IR and ¹H nuclear magnetic resonance spectra. Cytotoxicity of the compounds was demonstrated on cancer cell lines from liver (HUH7, FOCUS, MAHLAVU, HEPG2, HEP3B), breast (MCF7, BT20, T47D, CAMA-1), colon (HCT-116), gastric (KATO-3) and endometrial (MFE-296) cancer cell lines. Time-dependent cytotoxicity analysis of compound 5a indicated the long-term in situ stability of this compound. All compounds showed significant cell growth inhibitory activity on the selected cancer cell lines.

Due to the serious gastrointestinal side effects associated with prolonged use of current anti‐inflammatory therapies, various strategies such as the regulation of nitric oxide (NO) and prostaglandin E₂ (PGE₂) production have been explored in the field of anti‐inflammatory drug development. In this study, a series of disubstituted 1,3,4‐oxadiazoles (3a–f and 4a–f) and their cyclized 1,2,4‐triazole derivatives (5a–e and 6a–e) were synthesized and tested for their NO, PGE₂, and interleukin‐6 (IL‐6) releasing inhibition ability. All of the compounds were observed to reduce lipopolysaccharide (LPS)‐induced nitrite production in a concentration‐dependent manner. Moreover, compounds 3b (50 μM) and 6d (1 μM) exhibited 63% and 49% inhibition, respectively, while indomethacin showed 52% at 100 μM. Based on a preliminary NO inhibition assay, 10 of the compounds (3a, 3b, 3e, 4b, 4d, 6a–e) were selected to be evaluated for in vitro PGE₂, IL‐6, and inducible nitric oxide synthase (iNOS) inhibition. Notably, compound 6d proved to be the most active of the series with the lowest dose (1 µM), in comparison to the other further tested compounds (5–100 µM) and the reference drug indomethacin (100 µM). The inhibitory activity of the compounds was supported by docking simulations into the binding site of the iNOS protein receptor (Protein Data Bank [PDB]ID: 3E7G). The data showing that 4d reduced iNOS levels the most can be explained by the H‐bond with Tyr347 through oxadiazole and π–halogen interactions through the p‐bromo, in addition to aromatic interactions with protoporphyrin IX.

Several 5-(3,4-dichlorophenyl)-2-(aroylmethyl)thio-1,3,4-oxadiazoles were synthesized and characterized by elemental analyses, IR and nuclear magnetic resonance spectra. All compounds were evaluated for anti-inflammatory activity by determining their ability to provide protection against carregeenan-induced edema in rat paw. In addition, ulcerogenic activity was determined. The anti-inflammatory data scoring showed that compounds 5e, 5f and 5g, at the dose of 100 mg/kg, exhibited anti-inflammatory activity, which for compound 5f was comparable to that of the reference drug Indometacin (CAS 53-86-1).