Synthesis, Characterization, and Anti-Cancer Activity of Some New N'-(2-Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones Derivatives

Ayman El-Faham; Muhammad Farooq; Sherine N Khattab; Nael Abutaha; Mohammad A Wadaan; Hazem A Ghabbour; Hoong-Kun Fun

doi:10.3390/molecules200814638

Synthesis, Characterization, and Anti-Cancer Activity of Some New N'-(2-Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones Derivatives

Molecules. 2015 Aug 13;20(8):14638-55. doi: 10.3390/molecules200814638.

Authors

Ayman El-Faham^{1

2}, Muhammad Farooq³, Sherine N Khattab², Nael Abutaha⁴, Mohammad A Wadaan⁵, Hazem A Ghabbour⁶, Hoong-Kun Fun^{7

8}

Affiliations

¹ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. Sh.n.Khattab@gmail.com.
² Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Alexandria 21321, Egypt. Sh.n.Khattab@gmail.com.
³ Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. fmuhammad@ksu.edu.sa.
⁴ Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. nabutaha@ksu.edu.sa.
⁵ Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. Wadaan@ksu.edu.sa.
⁶ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. ghabbourh@yahoo.com.
⁷ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. hfun.c@ksu.edu.sa.
⁸ Crystallography Unit, School of Physics, Universiti Sains Malaysia, Penang 11800, Malaysia. hfun.c@ksu.edu.sa.

Abstract

Eight novel N'-(2-oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazone derivatives 4a-h were synthesized and fully characterized by IR, NMR ((1)H-NMR and (13)C-NMR), elemental analysis, and X-ray crystallography. The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay. The compounds 3e, 3f, 4a, 4c, and 4e revealed promising anti-cancer activities in tested human tumour cells lines (IC50 values between 3 and 7 μM) as compared to the known anti-cancer drug 5-Fluorouracil (IC50 32-50 μM). Among the tested compounds, 4a showed specificity against leukaemia (Jurkat) cells, with an IC50 value of 3.14 μM, but this compound was inactive in liver cancer and normal cell lines.

Keywords: anti-cancer activity; hydrazide-hydrazone; isatin; valproic acid.

Publication types

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

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology*
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Fluorouracil / pharmacology
HEK293 Cells
Hep G2 Cells
Humans
Hydrazones / chemical synthesis
Hydrazones / chemistry*
Hydrazones / pharmacology*
Isatin / analogs & derivatives*
Isatin / chemical synthesis
Isatin / chemistry
Isatin / pharmacology
Jurkat Cells
Valproic Acid / analogs & derivatives*
Valproic Acid / chemical synthesis
Valproic Acid / pharmacology

Substances

Antineoplastic Agents
Hydrazones
Valproic Acid
Isatin
Fluorouracil