Bis-isatin hydrazones with novel linkers: Synthesis and biological evaluation as cytotoxic agents

Hany S Ibrahim; Sahar M Abou-Seri; Nasser S M Ismail; Mahmoud M Elaasser; Mohamed H Aly; Hatem A Abdel-Aziz

doi:10.1016/j.ejmech.2015.11.047

Bis-isatin hydrazones with novel linkers: Synthesis and biological evaluation as cytotoxic agents

Eur J Med Chem. 2016 Jan 27:108:415-422. doi: 10.1016/j.ejmech.2015.11.047. Epub 2015 Dec 2.

Authors

Hany S Ibrahim¹, Sahar M Abou-Seri², Nasser S M Ismail³, Mahmoud M Elaasser⁴, Mohamed H Aly⁵, Hatem A Abdel-Aziz⁶

Affiliations

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt.
² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt. Electronic address: saharshaarawy_69@yahoo.com.
³ Pharmaceutical Chemistry Department, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University, Cairo 12311, Egypt.
⁴ The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo, Egypt.
⁵ Department of Pharmacology and Toxicology, Faculty of Pharmacy, British University in Egypt (BUE), Cairo, Egypt; Department of Biology, School of Sciences and Engineering (SSE), The American University in Cairo, 11835 New Cairo, Egypt.
⁶ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Department of Applied Organic Chemistry Department, National Research Center, Dokki, Cairo 12622, Egypt. Electronic address: hatem_741@yahoo.com.

PMID: 26706352
DOI: 10.1016/j.ejmech.2015.11.047

Abstract

Many bis-isatins and isatins with hydrazide extension were reported to have a potential anti-proliferative effects against different cancer cell lines and cancer targets. In this study, four series of bis-isatins with hydrazide linkers were synthesized. These compounds were investigated for their antitumor activity by assessing their cytotoxic potency against HepG2, MCF-7 and HCT-116 cancer cell lines. Compound 21c possessed significant cytotoxic activity against MCF-7 (IC50 = 1.84 μM) and HCT-116 (IC50 = 3.31 μM) that surpasses the activity of doxorubicin against both cell lines (MCF-7; IC50 = 2.57 μM and HCT-116; IC50 = 3.70 μM). Cell cycle analysis and annexin V-FITC staining of MCF-7 cells treated with 21c suggested that the cytotoxic effect of the compound could be attributed to its pro-apoptotic activity.

Keywords: Bis-isatin hydrazones; Cell cycle; Cytotoxic; Pro-apoptotic.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Cell Cycle / drug effects
Cell Proliferation / drug effects
Cytotoxins / chemical synthesis
Cytotoxins / chemistry
Cytotoxins / pharmacology*
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
HCT116 Cells
Hep G2 Cells
Humans
Hydrazones / chemical synthesis
Hydrazones / chemistry
Hydrazones / pharmacology*
Inhibitory Concentration 50
Isatin / analogs & derivatives
Isatin / chemistry
Isatin / pharmacology*
MCF-7 Cells
Molecular Structure
Structure-Activity Relationship

Substances

Antineoplastic Agents
Cytotoxins
Hydrazones
Isatin