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Dec, 2025;29 (6): 5129-5150.

Quinoline and quinolone carboxamides: A review of anticancer activity with detailed structure-activity relationship analysis.

Neethu Mariam Thomas, Majed Alharbi, Venkanna Muripiti, Janardhan Banothu
Author Information
  1. Neethu Mariam Thomas: Department of Chemistry, National Institute of Technology Calicut, Kozhikode, 673601, Kerala, India.
  2. Majed Alharbi: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
  3. Venkanna Muripiti: Department of Education, Central University of Kerala, Tejaswini Hills, Periye, Kasaragod, 671320, Kerala, India.
  4. Janardhan Banothu: Department of Chemistry, National Institute of Technology Calicut, Kozhikode, 673601, Kerala, India. janardhan@nitc.ac.in. ORCID
PMID: 39873887 DOI: 10.1007/s11030-024-11092-4

Abstract

Quinoline is a highly privileged scaffold with significant pharmacological potential. Introducing a carbonyl group into the quinoline ring generates a quinolone ring, which exhibits promising biological properties. Incorporating a carboxamide linkage at different positions within the quinoline and quinolone frameworks has proven an effective strategy for enhancing pharmacological properties, particularly anticancer potency. Consequently, various scientific communities have explored quinoline and quinolone carboxamides for their anticancer activities, introducing modifications at key positions. This review article aims to compile the anticancer activity of various quinoline and quinolone carboxamide derivatives, accompanied by a detailed structure-activity relationship (SAR) analysis. It also categorizes the data into activities of isolated/fused quinoline and quinolone carboxamide derivatives, which were further subclassified based on the mechanisms of anticancer action. Among the numerous derivatives studied, compounds 8, 19, 31, 34, 40, 68, 108, 116, and 132 have emerged as the most potent anticancer agents, making them strong candidates for further drug design and development. The mechanisms underlying the anticancer activity of these potent compounds have been identified as inhibitors of topoisomerase (8, 19, 31, and 34), protein kinase (40, 108, and 116), human dihydroorotate dehydrogenase (68), and as a cannabinoid receptor 2 agonist (132). We anticipate this review will be valuable to researchers engaged in the structural design and development of quinoline and quinolone carboxamide-based anticancer drugs with high efficacy.

Keywords

ATM kinase inhibitor Cannabinoid receptor inhibitor Human dihydroorotate dehydrogenase inhibitor Platelet-derived growth factor inhibitor Quinoline Topoisomerase inhibitor

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Grants

  1. GPIP: 1601-166-2024/Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, Saudi Arabia
  2. EEQ/2020/000303/Science and Engineering Research Board

MeSH Term

Quinolines
Humans
Antineoplastic Agents
Structure-Activity Relationship
Quinolones
Neoplasms
Animals

Chemicals

Quinolines
Antineoplastic Agents
Quinolones
quinoline
Journal Article Review

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