{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["10(35)"],"submitter":["Al-Ziyadi SH"],"pubmed_abstract":["

Background

Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a pivotal role in angiogenesis and tumor progression. Targeting VEGFR-2 remains a validated strategy for anticancer drug development.

Objective

This study aimed to design, synthesize, and evaluate a novel series of sulfonamide derivatives as potential VEGFR-2 inhibitors with anticancer activity.

Methods

A series of sulfonamide derivatives were synthesized through multistep organic reactions. Their structures were confirmed by spectroscopic methods. In vitro antiproliferative activity was evaluated against HCT-116, HepG-2, and MCF-7 cancer cell lines using MTT assays. Selectivity was assessed via cytotoxicity against normal WI-38 fibroblasts. Compounds showing potent anticancer activity were further examined for VEGFR-2 and EGFR kinase inhibition, cell cycle progression, and apoptosis induction. Molecular docking and in silico ADMET/toxicity analyses supported the pharmacological evaluation.

Results

Among the tested compounds, 3a, 6, and 15 exhibited potent cytotoxicity against all cancer cell lines, with compound 6 showing IC50 values of 3.53, 3.33, and 4.31 μM against HCT-116, HepG-2, and MCF-7, respectively. These compounds showed minimal cytotoxicity against WI-38 cells (IC50 > 69 μM), indicating favorable selectivity. Compound 15 exhibited the strongest VEGFR-2 inhibition (IC50 = 0.0787 μM), while compound 3a was the most potent EGFR inhibitor (IC50 = 0.17 μM). Flow cytometry revealed that compounds 3a, 6, and 15 induced G2/M and Pre-G1 phase arrest and significantly enhanced apoptosis. Docking studies demonstrated favorable binding interactions with VEGFR-2. ADMET predictions suggested acceptable drug-likeness and safety profiles.

Conclusion

Compounds 3a, 6, and 15 represent promising VEGFR-2-targeting sulfonamides with potent, selective anticancer activity and favorable pharmacokinetic and safety profiles, warranting further development as lead candidates."],"journal":["ACS omega"],"pagination":["39772-39790"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12423892"],"repository":["biostudies-literature"],"pubmed_title":["Novel Sulfonamide Derivatives as Anticancer Agents, VEGFR‑2 Inhibitors, and Apoptosis Triggers: Design, Synthesis, and Computational Studies."],"pmcid":["PMC12423892"],"pubmed_authors":["Hassan SM","Belal A","Mehany ABM","Al-Ziyadi SH","Al-Shareef HF","Abdelshafi NS","Elgammal WE","Albezrah NKA","Obaidullah AJ","Halawa AH"],"additional_accession":[]},"is_claimable":false,"name":"Novel Sulfonamide Derivatives as Anticancer Agents, VEGFR‑2 Inhibitors, and Apoptosis Triggers: Design, Synthesis, and Computational Studies.","description":"

Background

Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a pivotal role in angiogenesis and tumor progression. Targeting VEGFR-2 remains a validated strategy for anticancer drug development.

Objective

This study aimed to design, synthesize, and evaluate a novel series of sulfonamide derivatives as potential VEGFR-2 inhibitors with anticancer activity.

Methods

A series of sulfonamide derivatives were synthesized through multistep organic reactions. Their structures were confirmed by spectroscopic methods. In vitro antiproliferative activity was evaluated against HCT-116, HepG-2, and MCF-7 cancer cell lines using MTT assays. Selectivity was assessed via cytotoxicity against normal WI-38 fibroblasts. Compounds showing potent anticancer activity were further examined for VEGFR-2 and EGFR kinase inhibition, cell cycle progression, and apoptosis induction. Molecular docking and in silico ADMET/toxicity analyses supported the pharmacological evaluation.

Results

Among the tested compounds, 3a, 6, and 15 exhibited potent cytotoxicity against all cancer cell lines, with compound 6 showing IC50 values of 3.53, 3.33, and 4.31 μM against HCT-116, HepG-2, and MCF-7, respectively. These compounds showed minimal cytotoxicity against WI-38 cells (IC50 > 69 μM), indicating favorable selectivity. Compound 15 exhibited the strongest VEGFR-2 inhibition (IC50 = 0.0787 μM), while compound 3a was the most potent EGFR inhibitor (IC50 = 0.17 μM). Flow cytometry revealed that compounds 3a, 6, and 15 induced G2/M and Pre-G1 phase arrest and significantly enhanced apoptosis. Docking studies demonstrated favorable binding interactions with VEGFR-2. ADMET predictions suggested acceptable drug-likeness and safety profiles.

Conclusion

Compounds 3a, 6, and 15 represent promising VEGFR-2-targeting sulfonamides with potent, selective anticancer activity and favorable pharmacokinetic and safety profiles, warranting further development as lead candidates.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-01T23:32:52.418Z","creation":"2026-05-24T03:07:07.121Z"},"accession":"S-EPMC12423892","cross_references":{"pubmed":["40949276"],"doi":["10.1021/acsomega.5c03503"]}}