2. Academic Validation
  3. Pharmacological investigation of new niclosamide-based isatin hybrids as antiproliferative, antioxidant, and apoptosis inducers

Pharmacological investigation of new niclosamide-based isatin hybrids as antiproliferative, antioxidant, and apoptosis inducers

  • Sci Rep. 2024 Aug 27;14(1):19818. doi: 10.1038/s41598-024-69250-5.
Mervat M Omran 1,  Mona M Kamal 2,  Yousry A Ammar 3,  Moustafa S Abusaif 3,  Magda M F Ismail 4,  Heba H Mansour 5
Affiliations

Affiliations

  • 1 Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
  • 2 Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
  • 3 Department of Chemistry, Faculty of Science (Boys), Al-Azhar University, Nasr City, Cairo, 11884, Egypt.
  • 4 Department of Medicinal Pharmaceutical Chemistry and Drug Design, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City, Cairo, 11754, Egypt.
  • 5 Health Radiation Research Department, National Centre for Radiation Research and Technology, Egyptian Atomic Energy Authority, P.O. Box 29, Nasr City Cairo, Egypt. hebahosny@hotmail.com.
PMID: 39191850 DOI: 10.1038/s41598-024-69250-5
Abstract

A group of Niclosamide-linked isatin hybrids (Xo, X1, and X2) was created and examined using IR, 1HNMR, 13C NMR, and mass spectrometry. These hybrids' cytotoxicity, antioxidant, cell cycle analysis, and apoptosis-inducing capabilities were identified. Using the SRB assay, their cytotoxicity against the human HCT-116, MCF-7, and HEPG-2 Cancer cell lines, as well as VERO (African Green Monkey Kidney), was evaluated. Compound X1 was the most effective compound. In HCT-116 cells, compound X1 produced cell cycle arrest in the G1 phase, promoted cell death, and induced Apoptosis through mitochondrial membrane potential breakdown in comparison to niclosamide and the control. Niclosamide and compound X1 reduced Reactive Oxygen Species generation and modulated the gene expression of Bax, Bcl-2, Bcl-xL, and PAR-4 in comparison to the control. Docking modeling indicated their probable binding modalities with the XIAP BIR2 domain, which selectively binds Caspase-3/7, and highlighted their structural drivers of activity for further optimization investigations. Computational in silico modeling of the new hybrids revealed that they presented acceptable physicochemical values as well as drug-like characteristics, which may introduce them as drug-like candidates. The study proved that compound X1 might be a novel candidate for the development of Anticancer agents as it presents antiproliferative activity mediated by Apoptosis.

Keywords

Antioxidant; Apoptosis; Cell cycle; Cytotoxicity; Molecular docking; Niclosamide analogue synthesis.

Figures
Products