Synthesis, cytotoxic evaluation, and molecular docking studies of some new 1, 3, 4-oxadiazole-based compounds

Abstract

Background and purpose: Oxadiazole-derived compounds have been shown to have a wide range of pharmacological activities. 2, 5-Disubstituted 1, 3, 4-oxadiazole derivatives have occupied a specific place in the design of anti-proliferative agents. In the present work a series of 2, 5-disubstituted 1, 3, 4-oxadiazoles derivatives containing amide group has been synthesized via a two-step reaction. Experimental approach: A mixture of substituted carboxylic acid derivatives, semicarbazide, and phosphorus oxychloride in reflux condition yielded 2-amino-5-aryl-1, 3, 4-oxadiazole derivatives. Acylation of the amino group of the resultant oxadiazole with 6-chloronicotinoyl chloride in dry tetrahydrofuran/pyridine afforded the final products. The synthesized molecules were docked in the active sites of the epidermal growth factor receptor tyrosine kinase domain (PDB: 1M17) crystal structure to study the possible interactions with the active site. Cytotoxic activities of final products against HeLa and MCF-7 cells were also assessed by MTT assay. Findings/Results: Compounds IIb, IIc, and IIe had a considerable cytotoxic activity with IC50 values of 19.9, 35, and 25.1 μM, respectively against HeLa cells. The highest docking score was -7.89 kcal/mol for compound IIe . Conclusion and implications: Compound IIe exhibited remarkable cytotoxic activity against the two tested cell lines particularly HeLa cells which was in accordance with the in silico ΔG bind result but further evaluations are necessary to prove these findings.

Synthesis and cytotoxic activity evaluation of some new 1, 3, 4-oxadiazole, 1, 3, 4-thiadiazole and 1, 2, 4- triazole derivatives attached to phthalimide

“…In the light of reported cytotoxic activity of azoles ( 7 9 40 ), cyclic imides, and conjugated azole-imide ( 24 25 ), and in continuing efforts to develop potent cytotoxic agents, some phthalimide-based azoles including S-CH2CONH-linker were designed and prepared after exploring molecular hybridization approaches in a three-step procedure as depicted in Schemes 1 and 2. Molecular hybridization is one of the useful approaches in the design of new therapeutic compounds.…”

Synthesis, Cytotoxic Effect Assessment and Molecular Docking Studies of Disubstituted Thiadiazole Including Oxadiazole as Hybrid Component

“…To evaluate cell survival, treated cells were incubated with 20 µL of MTT solution for 4 h, afterwards, medium was thrown out,formazan crystals were dissolved by dimethyl sulfoxide (150µL). The absorbance was measured at 540 nm using an ELISA plate reader [11,18,19]. The experiments were accomplished in triplicate.…”

“…The proposed anti-cancer mechanisms for thiadiazole include: potent Abl tyrosine kinase inhibitors [5], anti-tubulin agents [8]. Recent findings in the identification of epidermal growth factor receptor (EGFR) inhibitors may create hope for cancer treatment [9].Similarly, 1, 3, 4-oxadiazole derivatives are correlated with many types of biological virtues especially anticancer effects [8][9][10][11]. There are various reports citing oxadiazole as potential cytotoxic agent [4].…”

“…Adamantine scaffold containing 1, 3, 4-thiadiazole derivatives were synthesized and evaluated against both wild EGFR and mutant EGFR by Wassel et al [14]. Due to the reported inhibitory effects of oxadiazole and thiadiazole derivatives on kinases (1,11,13,15), especially tyrosine kinase [14,16], molecular docking studies of final compounds on binding sites of the EGFR tyrosine kinase domain (PDB: 1M17) crystal structure were also performed and their binding energies were calculated.…”

Antioxidant properties of butylated phenol with oxadiazole and hydrazone moiety atorthoposition supported by DFT study

“… 28 It is interesting to note that substituted groups may also influence the scavenging ability of such compounds, as mentioned previously, which indicates the existence of a close relationship between chemical structure and the ability to scavenge free radicals. The 1,3,4-oxadiazoles and their 2,5-disubstituted derivatives function well as development materials due to their large spectrum of various biological activities, such as anti-inflammatory, 29 anticancer, 30 antibacterial, 31 antifungal, 18 antihypertensive, 32 antitubercular, 33 anti-HIV 34 and antioxidant activities. 35 Moreover, some oxadiazoles derivatives have exhibited antioxidant activities even though they do not contain any phenol group.…”