Novel Bis(2-cyanoacrylamide) Linked to Sulphamethoxazole: Synthesis, DNA Interaction, Anticancer, ADMET, Molecular Docking, and DFT Studies.

Autor: Ragheb MA; Department of Chemistry (Biochemistry Division), Faculty of Science, Cairo University, Giza, 12613, Egypt., Mohamed FG; Department of Chemistry (Biochemistry Division), Faculty of Science, Cairo University, Giza, 12613, Egypt., Diab HM; Department of Chemistry, Faculty of Science, Cairo University, Giza, 12613, Egypt., Ragab MS; Department of Chemistry, Faculty of Science, Cairo University, Giza, 12613, Egypt., Emara M; Center for Aging and Associated Diseases, Zewail City of Science, Technology and innovation, 12578-, Giza, Egypt., Elwahy AHM; Department of Chemistry, Faculty of Science, Cairo University, Giza, 12613, Egypt., Abdelhamid IA; Department of Chemistry, Faculty of Science, Cairo University, Giza, 12613, Egypt., Soliman MH; Department of Chemistry (Biochemistry Division), Faculty of Science, Cairo University, Giza, 12613, Egypt.
Jazyk: angličtina
Zdroj: Chemistry & biodiversity [Chem Biodivers] 2024 Apr; Vol. 21 (4), pp. e202301341. Date of Electronic Publication: 2024 Mar 08.
DOI: 10.1002/cbdv.202301341
Abstrakt: In the light of advancement and potential extensive use of medication design and therapy, new bis(cyanoacrylamides) incorporating sulphamethoxazole derivatives (7 a-7 f) were synthesized and confirmed by different spectral tools. In vitro anticancer activity towards different human cancer cells (HCT116, MDA-MB-231 and A549) was assessed using MTT assay. Among all derivatives, 4C- and 6C-spacer derivatives (7 e and 7 f) had the most potent growth inhibitory activities against HCT116 cells with IC 50 values of 39.7 and 28.5 μM, respectively. 7 e and 7 f induced apoptosis and suppressed migration of HCT116 cells. These compounds also induced a significant increase in caspase-3 and CDH1 activities, and a downregulation of Bcl2 using ELISA. pBR322 DNA cleavage activities of cyanoacrylamides were determined using agarose gel electrophoresis. Furthermore, 7 e and 7 f showed good DNA and BSA binding affinities using different spectroscopic techniques. Furthermore, molecular docking for 7 e and 7 f was performed to anticipate their binding capabilities toward various proteins (Bcl2, CDH1 and BSA). The docking results were well correlated with those of experimental results. Additionally, density functional theory and ADMET study were performed to evaluate the molecular and pharmacokinetic features of 7 e and 7 f, respectively. Thus, this work reveals promising antitumor lead compounds that merit future research and activity enhancement.
(© 2024 Wiley‐VHCA AG, Zurich, Switzerland.)
Databáze: MEDLINE
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