Nicotinonitriles-based therapeutics as versatile pharmacophores in rational anticancer drug design.
9 affiliations
- 1Department of Chemistry, College of Sciences, University of Sharjah Sharjah 27272 United Arab Emirates [email protected].
- 2Bioinformatics and Functional Genomics Research Group, Research Institute of Sciences and Engineering (RISE), University of Sharjah Sharjah 27272 United Arab Emirates.
- 3Chemistry Department, Faculty of Science, Suez Canal University Ismailia 41522 Egypt.
- 4Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University-Egypt New Damietta 34518 Egypt.
- 5Department of Pharmacy, Institute of Pharmaceutics and Biopharmaceutics, Marburg University Robert-Koch-Str. 4 35037 Marburg Germany [email protected].
- 6Pest Physiology Department, Plant Protection Research Institute, Agricultural Research Center Giza 12311 Egypt.
- 7Department of Medicinal Chemistry, Faculty of Pharmacy, Galala University New Galala 43713 Egypt [email protected].
- 8Medicinal Chemistry Department, Faculty of Pharmacy, Suez Canal University Ismailia 41522 Egypt.
- 9Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University Ismailia 41522 Egypt.
Abstract
Nicotinonitriles (3-cyanopyridine-based compounds) are emerging as privileged frameworks in rational anticancer drug discovery due to their distinctive electronic properties, metabolic stability, and diverse pharmacological profiles. This review discusses recent developments in nicotinonitrile-derived agents as effective kinase inhibitors of EGFR, VEGFR-2, HER2, CDKs, c-Met, BRAF, and PIM kinases, among others. By discussing mono-, bi-, and multi-target inhibitors, the mechanisms of action are reviewed, with adaptations to induce apoptosis, arrest the cell cycle, and reverse drug resistance. Many clinical and preclinical candidates are nanomolar to sub-micromolar in equipotency across multiple cancer models. The substitution at the core of nicotinonitrile improves targeted selectivity, drug-like properties, and the safety profile, and is a key toward next-generation anticancer agents. Moreover, the review presents information on enzyme-mediated inhibition, hybrid construction, and molecular docking that strengthen the scaffold's potential for ecotoxicological pipelines. Overall, nicotinonitrile-based derivatives seem to be an attractive nucleus for multi-target drug discovery, with a broad therapeutic spectrum in cancer management.
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BibTeX
@article{nafie2026nicotinonitrilesbased,
title = {{Nicotinonitriles-based therapeutics as versatile pharmacophores in rational anticancer drug design.}},
author = {Mohamed S Nafie and Mohamed A Zeidan and Sherif Ashraf Fahmy and Mohamed K Diab and Khaled M Darwish and Asmaa S A Yassen},
journal = {RSC advances},
year = {2026},
month = oct,
doi = {10.1039/d6ra05778k},
url = {https://europepmc.org/article/MED/42910047},
note = {CC BY},
}
RIS
TY - JOUR
TI - Nicotinonitriles-based therapeutics as versatile pharmacophores in rational anticancer drug design.
AU - Mohamed S Nafie
AU - Mohamed A Zeidan
AU - Sherif Ashraf Fahmy
AU - Mohamed K Diab
AU - Khaled M Darwish
AU - Asmaa S A Yassen
PY - 2026
DA - 2026/10/21
JO - RSC advances
DO - 10.1039/d6ra05778k
UR - https://europepmc.org/article/MED/42910047
AB - Nicotinonitriles (3-cyanopyridine-based compounds) are emerging as privileged frameworks in rational anticancer drug discovery due to their distinctive electronic properties, metabolic stability, and diverse pharmacological profiles. This review discusses recent developments in nicotinonitrile-derived agents as effective kinase inhibitors of EGFR, VEGFR-2, HER2, CDKs, c-Met, BRAF, and PIM kinases, among others. By discussing mono-, bi-, and multi-target inhibitors, the mechanisms of action are reviewed, with adaptations to induce apoptosis, arrest the cell cycle, and reverse drug resistance. Many clinical and preclinical candidates are nanomolar to sub-micromolar in equipotency across multiple cancer models. The substitution at the core of nicotinonitrile improves targeted selectivity, drug-like properties, and the safety profile, and is a key toward next-generation anticancer agents. Moreover, the review presents information on enzyme-mediated inhibition, hybrid construction, and molecular docking that strengthen the scaffold's potential for ecotoxicological pipelines. Overall, nicotinonitrile-based derivatives seem to be an attractive nucleus for multi-target drug discovery, with a broad therapeutic spectrum in cancer management.
SN - 2046-2069
ER -