Exploiting the 4-hydrazinobenzoic acid moiety for the development of anticancer agents: Synthesis and biological profile

Hatem A Abuelizz; Hanem M Awad; Mohamed Marzouk; Fahd A Nasr; Ahmed H Bakheit; Ahmed M Naglah; Nasser S Al-Shakliah; Rashad Al-Salahi

doi:10.1016/j.bioorg.2020.104098

Exploiting the 4-hydrazinobenzoic acid moiety for the development of anticancer agents: Synthesis and biological profile

Bioorg Chem. 2020 Sep:102:104098. doi: 10.1016/j.bioorg.2020.104098. Epub 2020 Jul 14.

Authors

Hatem A Abuelizz¹, Hanem M Awad², Mohamed Marzouk², Fahd A Nasr³, Ahmed H Bakheit⁴, Ahmed M Naglah⁵, Nasser S Al-Shakliah¹, Rashad Al-Salahi⁶

Affiliations

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
² Department of Tanning Materials and Leather Technology, National Research Centre, 33 El-Bohouth St. (Former El-Tahrir St.), Dokki, Cairo 12622, Egypt.
³ Medicinal Aromatic, and Poisonous Plants Research Center, College of Pharmacy, King Saud University, PO Box 2457, Riyadh, 11451, Saudi Arabia.
⁴ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia; Department of Chemistry, Faculty of Science and Technology, El-Neelain University, P.O. Box 12702, Khartoum 11121, Sudan.
⁵ Department of Pharmaceutical Chemistry, Drug Exploration and Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; Peptide Chemistry Department, Chemical Industries Research Division, National Research Centre, 33 El-Bohouth St. (Former El-Tahrir St.), Dokki, Cairo 12622, Egypt.
⁶ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia. Electronic address: ralsalahi@ksu.edu.sa.

PMID: 32702510
DOI: 10.1016/j.bioorg.2020.104098

Abstract

Thirteen 4-hydrazinobenzoic acid derivatives were elaborated and characterized by spectral analyses (NMR and MS). Evaluation of their in vitro cytotoxic activity showed that some of the targets demonstrated potent inhibitory effects against HCT-116 and MCF-7 cancer cells. The IC₅₀ values ranged between 21.3 ± 4.1 and 28.3 ± 5.1 µM, respectively, whereas those of doxorubicin (reference drug) ranged between 22.6 ± 3.9 and 19.7 ± 3.1 µM, respectively. The active targets 6, 7 and 9 exhibited very weak cytotoxicity on normal cells (RPE-1) and showed higher IC₅₀ values against HCT-116 and MCF-7 cells in comparison to doxorubicin. Furthermore, compounds 7, 9 and 10 inhibited the proliferation of MCF-7 by the induction of apoptosis. The bioassay results in the regression plots generated in 3D QSAR models were in agreement and correlated with the anticancer results of the target molecules. The 4-hydazinobenzoic acid derivatives can be used as cornerstones for further structural modifications as future anticancer agents.

Keywords: 3D QSAR; 4-Hydrazinobenzoic acid; Anticancer; Apoptosis; MTT assay.

Publication types

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

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Benzoates / chemical synthesis
Benzoates / chemistry
Benzoates / pharmacology*
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Development*
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Quantitative Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Antineoplastic Agents
Benzoates
4-hydrazinobenzoic acid