Volume 17, Issue 8 e202100736
Review

Contribution of Knoevenagel Condensation Products toward the Development of Anticancer Agents: An Updated Review

Dr. Ramya Tokala

Dr. Ramya Tokala

Department of Medicinal Chemistry, National Institution of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037 India

These authors contributed equally to this work.

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Darshana Bora

Darshana Bora

Department of Medicinal Chemistry, National Institution of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037 India

These authors contributed equally to this work.

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Dr. Nagula Shankaraiah

Corresponding Author

Dr. Nagula Shankaraiah

Department of Medicinal Chemistry, National Institution of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037 India

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First published: 28 February 2022
Citations: 9

Graphical Abstract

Expanding on condensation: The Knoevenagel condensation is an entrenched, prevailing, prominent arsenal following greener principles in the generation of α,β-unsaturated ketones involving carbonyl functionality and active methylenes. This review compiles the efficiency of the Knoevenagel condensation to generate molecules of pharmacological interest, predominantly toward cancer.

Abstract

Knoevenagel condensation is an entrenched, prevailing, prominent arsenal following greener principles in the generation of α, β-unsaturated ketones/carboxylic acids by involving carbonyl functionalities and active methylenes. This reaction has proved to be a major driving force in many multicomponent reactions indicating the prolific utility toward the development of biologically fascinating molecules. This eminent reaction was acclimatised on different pharmacophoric aldehydes (benzimidazole, β-carboline, phenanthrene, indole, imidazothiadiazole, pyrazole etc.) and active methylenes (oxindole, barbituric acid, Meldrum's acid, thiazolidinedione etc.) to generate the library of chemical compounds. Their potential was also explicit to understand the significance of functionalities involved, which thereby evoke further developments in drug discovery. Furthermore, most of these reaction products exhibited remarkable anticancer activity in nanomolar to micromolar ranges by targeting different cancer targets like DNA, microtubules, Topo-I/II, and kinases (PIM, PARP, NMP, p300/CBP) etc. This review underscores the efficiency of the Knoevenagel condensation explored in the past six-year to generate molecules of pharmacological interest, predominantly toward cancer. The present review also provides the aspects of structure-activity relationships, mode of action and docking study with possible interaction with the target protein.

Conflict of interest

The authors declare no conflict of interest.