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Privileged Heterocyclic Scaffolds in Anticancer Drug Development

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 4202

Special Issue Editor

Special Issue Information

Dear colleagues,

Several heterocyclic scaffolds, such as quinoline, benzimidazole, pyrazole, or indole, are considered privileged structures in the design of anticancer drugs. Due to their drug-like properties, these scaffolds are widely used in rational drug design and they can be found within a large variety of approved anticancer drugs. Of most interest are the scaffolds that have selectivity for a small group of closely related targets. This type of scaffold can generate compounds with high selectivity towards targets involved in cancer pathology, highlighting their importance in the development of selective antitumor drugs. The target-family privileged scaffold concept emerged to describe chemical frameworks that are specific for a single target family and with limited off-target affinities.

This Special Issue aims to provide a survey of the recent advances in the use of privileged heterocyclic scaffolds for targeted anticancer drug development. Special emphasis should be placed on the selective affinity of the heterocyclic scaffold towards a particular type of oncotarget. Either original research articles or reviews that discuss the anticancer applications of selective molecular scaffolds are welcome.

Dr. George Mihai Nitulescu
Guest Editor

Manuscript Submission Information

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Keywords

  • Privileged scaffolds
  • Targeted drug design
  • Anticancer drugs
  • Medicinally privileged heterocycles

Published Papers (2 papers)

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Research

13 pages, 3411 KiB  
Article
Quantitative and Qualitative Analysis of the Anti-Proliferative Potential of the Pyrazole Scaffold in the Design of Anticancer Agents
Molecules 2022, 27(10), 3300; https://doi.org/10.3390/molecules27103300 - 20 May 2022
Cited by 9 | Viewed by 1383
Abstract
The current work presents an objective overview of the impact of one important heterocyclic structure, the pyrazole ring, in the development of anti-proliferative drugs. A set of 1551 pyrazole derivatives were extracted from the National Cancer Institute (NCI) database, together with their growth [...] Read more.
The current work presents an objective overview of the impact of one important heterocyclic structure, the pyrazole ring, in the development of anti-proliferative drugs. A set of 1551 pyrazole derivatives were extracted from the National Cancer Institute (NCI) database, together with their growth inhibition effects (GI%) on the NCI’s panel of 60 cancer cell lines. The structures of these derivatives were analyzed based on the compounds’ averages of GI% values across NCI-60 cell lines and the averages of the values for the outlier cells. The distribution and the architecture of the Bemis–Murcko skeletons were analyzed, highlighting the impact of certain scaffold structures on the anti-proliferative effect’s potency and selectivity. The drug-likeness, chemical reactivity and promiscuity risks of the compounds were predicted using AMDETlab. The pyrazole ring proved to be a versatile scaffold for the design of anticancer drugs if properly substituted and if connected with other cyclic structures. The 1,3-diphenyl-pyrazole emerged as a useful scaffold for potent and targeted anticancer candidates. Full article
(This article belongs to the Special Issue Privileged Heterocyclic Scaffolds in Anticancer Drug Development)
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17 pages, 3387 KiB  
Article
Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Tri-Aryl Imidazole-Benzene Sulfonamide Hybrids as Promising Selective Carbonic Anhydrase IX and XII Inhibitors
Molecules 2021, 26(16), 4718; https://doi.org/10.3390/molecules26164718 - 04 Aug 2021
Cited by 4 | Viewed by 1832
Abstract
A novel series of tri-aryl imidazole derivatives 5an carrying benzene sulfonamide moiety has been designed for their selective inhibitory against hCA IX and XII activity. Six compounds were found to be potent and selective CA IX inhibitors with the order of [...] Read more.
A novel series of tri-aryl imidazole derivatives 5an carrying benzene sulfonamide moiety has been designed for their selective inhibitory against hCA IX and XII activity. Six compounds were found to be potent and selective CA IX inhibitors with the order of 5g > 5b > 5d > 5e > 5g > 5n (Ki = 0.3–1.3 μM, and selectivity ratio for hCA IX over hCA XII = 5–12) relative to acetazolamide (Ki = 0.03 μM, and selectivity ratio for hCA IX over hCA XII = 0.20). The previous sixth inhibitors have been further investigated for their anti-proliferative activity against four different cancer cell lines using MTT assay. Compounds 5g and 5b demonstrated higher antiproliferative activity than other tested compounds (with GI50 = 2.3 and 2.8 M, respectively) in comparison to doxorubicin (GI50 = 1.1 M). Docking studies of these two compounds adopted orientation and binding interactions with a higher liability to enter the active side pocket CA-IX selectively similar to that of ligand 9FK. Molecular modelling simulation showed good agreement with the acquired biological evaluation. Full article
(This article belongs to the Special Issue Privileged Heterocyclic Scaffolds in Anticancer Drug Development)
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