Development of Isatin-Based Schiff Bases Targeting VEGFR-2 Inhibition: Synthesis, Characterization, Antiproliferative Properties, and QSAR Studies

Israa A. Seliem, Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, 44519, Zagazig, Egypt.
Siva S. Panda, Department of Chemistry and Physics, Augusta University, 30912, Augusta, GA, USA.
Adel S. Girgis, Department of Pesticide Chemistry, National Research Centre, Dokki, 12622, Giza, Egypt.
Queen L. Tran, Department of Chemistry and Physics, Augusta University, 30912, Augusta, GA, USA.
Mona F. Said, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, 11562, Cairo, Egypt.
Mohamed S. Bekheit, Department of Pesticide Chemistry, National Research Centre, Dokki, 12622, Giza, Egypt.
Anwar Abdelnaser, Institute of Global Health and Human Ecology, School of Sciences and Engineering, The American University in Cairo (AUC), 11835, Cairo, Egypt.
Soad Nasr, Institute of Pharmacology of Natural Products & Clinical Pharmacology, Ulm University, 89081, Ulm, Germany.
Walid Fayad, Drug Bioassay-Cell Culture Laboratory, Pharmacognosy Department, National Research Centre, Dokki, 12622, Giza, Egypt.
Ahmed A. Soliman, Drug Bioassay-Cell Culture Laboratory, Pharmacognosy Department, National Research Centre, Dokki, 12622, Giza, Egypt.
Rajeev Sakhuja, Department of Chemistry, Birla Institute of Technology and Science, Pilani, India.
Tarek S. Ibrahim, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, 21589, Jeddah, Saudi Arabia.
Zakaria K. Abdel-Samii, Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, 44519, Zagazig, Egypt.
Amany M. Al-Mahmoudy, Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, 44519, Zagazig, Egypt.

Fifth Author's Department

Institute of Global Health & Human Ecology

Document Type

Research Article

Publication Title

ChemMedChem

Publication Date

7-5-2022

doi

10.1002/cmdc.202200164

Abstract

Three sets of isatin-based Schiff bases were synthesized utilizing the molecular hybridization approach. Some of the synthesized Schiff bases show significant to moderate antiproliferative properties against MCF7 (breast), HCT116 (colon), and PaCa2 (pancreatic) cancer cell lines with potency compared to reference drugs 5-fluorouracil (5-FU) and Sunitinib. Among all, compound 17 f (3-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)imino)-1-((1-(2-methoxyphenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methylindolin-2-one) exhibits promising antiproliferative properties against the MCF7 cancer cell line with 2.1-fold more potency than Sunitinib. However, among all the synthesized compounds, three (5-methylisatin derivatives) were the most effective against HCT116 in comparison to 5-FU. Compound 17 f exhibited the highest anti-angiogenic effect on the vasculature as it significantly reduced BV from 43 mm to 2 mm in comparison to 5.7 mm for Sunitinib and flow cytometry supports the arrest of the cell cycle at G1/S phases. In addition, compound 17 f also showed high VEGFR-2 inhibition properties against breast cancer cell lines. Robust 2D-QSAR studies supported the biological data.

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e202200164

Last Page

e202200164

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