Design, synthesis and biological evaluation of novel indole-based oxalamide and aminoacetamide derivatives as tubulin polymerization inhibitors

Diao, Peng-Cheng; Jian, Xie-Er; Chen, Peng; Huang, Chuan; Yin, Jie; Huang, Jie; Li, Junsheng; Zhao, Pei‐Liang

doi:10.1016/j.bmcl.2019.126816

Cited by 22 publications

(20 citation statements)

References 23 publications

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“…We assembled a dataset of 851 compounds tested as Tub-Mts inhibitors and with reported bioactivity in different cancer cell lines [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. All compounds were retrieved from original and review articles and patents over a period of 15 years (2005–2020).…”

Section: Methodsmentioning

confidence: 99%

Tubulin Inhibitors: A Chemoinformatic Analysis Using Cell-Based Data

2021

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Inhibiting the tubulin-microtubules (Tub-Mts) system is a classic and rational approach for treating different types of cancers. A large amount of data on inhibitors in the clinic supports Tub-Mts as a validated target. However, most of the inhibitors reported thus far have been developed around common chemical scaffolds covering a narrow region of the chemical space with limited innovation. This manuscript aims to discuss the first activity landscape and scaffold content analysis of an assembled and curated cell-based database of 851 Tub-Mts inhibitors with reported activity against five cancer cell lines and the Tub-Mts system. The structure–bioactivity relationships of the Tub-Mts system inhibitors were further explored using constellations plots. This recently developed methodology enables the rapid but quantitative assessment of analog series enriched with active compounds. The constellations plots identified promising analog series with high average biological activity that could be the starting points of new and more potent Tub-Mts inhibitors.

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Section: Methodsmentioning

confidence: 99%

Tubulin Inhibitors: A Chemoinformatic Analysis Using Cell-Based Data

2021

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“…Also, 28 made stable interaction in the colchicine-binding of tubulin. These results encouraged further investigation on 28 to develop into new anti-cancer agents 69 .…”

Section: Indole As Anticancer Drugsmentioning

confidence: 97%

Target-based anticancer indole derivatives and insight into structure‒activity relationship: A mechanistic review update (2018–2021)

Dhiman

Sharma

Singh

2022

Acta Pharmaceutica Sinica B

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“…The molecular hybridization of these compounds has been reported as potential tubulin polymerization inhibitors [ 136 ]. Based on previous research on nicotinic acid and pyrazoline, Chen and colleagues [ 137 ] envisage that the amalgamation of indole, nicotinic acid, and pyrazoline will improve tubulin inhibitory activity. Hence, twenty-five nicotinoyl pyrazoline derivatives bearing N -methyl indole were synthesized ( 161 ).…”

Section: Indole Hybridsmentioning

confidence: 99%

A Review of the Recent Developments of Molecular Hybrids Targeting Tubulin Polymerization

Ebenezer

Shapi

Tuszyński

2022

IJMS

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Microtubules are cylindrical protein polymers formed from αβ-tubulin heterodimers in the cytoplasm of eukaryotic cells. Microtubule disturbance may cause cell cycle arrest in the G2/M phase, and anomalous mitotic spindles will form. Microtubules are an important target for cancer drug action because of their critical role in mitosis. Several microtubule-targeting agents with vast therapeutic advantages have been developed, but they often lead to multidrug resistance and adverse side effects. Thus, single-target therapy has drawbacks in the effective control of tubulin polymerization. Molecular hybridization, based on the amalgamation of two or more pharmacophores of bioactive conjugates to engender a single molecular structure with enhanced pharmacokinetics and biological activity, compared to their parent molecules, has recently become a promising approach in drug development. The practical application of combined active scaffolds targeting tubulin polymerization inhibitors has been corroborated in the past few years. Meanwhile, different designs and syntheses of novel anti-tubulin hybrids have been broadly studied, illustrated, and detailed in the literature. This review describes various molecular hybrids with their reported structural–activity relationships (SARs) where it is possible in an effort to generate efficacious tubulin polymerization inhibitors. The aim is to create a platform on which new active scaffolds can be modeled for improved tubulin polymerization inhibitory potency and hence, the development of new therapeutic agents against cancer.

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Design, synthesis and biological evaluation of novel indole-based oxalamide and aminoacetamide derivatives as tubulin polymerization inhibitors

Cited by 22 publications

References 23 publications

Tubulin Inhibitors: A Chemoinformatic Analysis Using Cell-Based Data

Tubulin Inhibitors: A Chemoinformatic Analysis Using Cell-Based Data

Target-based anticancer indole derivatives and insight into structure‒activity relationship: A mechanistic review update (2018–2021)

A Review of the Recent Developments of Molecular Hybrids Targeting Tubulin Polymerization

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