Synthesis and biological evaluation of substituted N-(2-(1H-benzo[d]imidazol-2-yl)phenyl)cinnamides as tubulin polymerization inhibitors

Donthiboina, Kavitha; Anchi, Pratibha; Gurram, Sowmyasree; Mani, Ganesh Kumar; Lakshmi, Uppu Jaya; Godugu, Chandraiah; Shankaraiah, Nagula; Kamal, Ähmed

doi:10.1016/j.bioorg.2020.104191

Cited by 32 publications

(12 citation statements)

References 41 publications

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“…This mechanism of action for new antiproliferative and anti-tubulin agents was also explored in the design of a new series of benzimidazole, based on the amalgamation of different pharmacophores as shown in Figure 16 . Twenty-five novel hybrids of benzimidazole combined with pyrazole 48 were reported by Wang et al [ 51 ]. The compounds were evaluated against four cancer cell lines.…”

Section: Benzimidazole 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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Section: Benzimidazole Hybridsmentioning

confidence: 99%

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

Ebenezer

Shapi

Tuszyński

2022

IJMS

View full text Add to dashboard Cite

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“…At a concentration of 2 µM, compound 20 caused the accumulation of A549 cells in the G 2 /M phase of the cell cycle. Donthiboina et al synthesized benzimidazole-cinnamide derivatives as potential tubulin polymerization inhibitors and evaluated their activity against A549, MDA-MB-231, B16F10, BT474, and 4T1 cell lines [41]. Among the synthesized compounds, 21 displayed IC 50 values in the range between 0.29 to 1.48 µM against the cancer cell lines tested, exhibiting the greatest potency against A549 cells.…”

Section: Imidazoles As Tubulin Polymerization Inhibitorsmentioning

confidence: 99%

Imidazoles as Potential Anticancer Agents: An Update on Recent Studies

et al. 2021

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Nitrogen-containing heterocyclic rings are common structural components of marketed drugs. Among these heterocycles, imidazole/fused imidazole rings are present in a wide range of bioactive compounds. The unique properties of such structures, including high polarity and the ability to participate in hydrogen bonding and coordination chemistry, allow them to interact with a wide range of biomolecules, and imidazole-/fused imidazole-containing compounds are reported to have a broad spectrum of biological activities. This review summarizes recent reports of imidazole/fused imidazole derivatives as anticancer agents appearing in the peer-reviewed literature from 2018 through 2020. Such molecules have been shown to modulate various targets, including microtubules, tyrosine and serine-threonine kinases, histone deacetylases, p53-Murine Double Minute 2 (MDM2) protein, poly (ADP-ribose) polymerase (PARP), G-quadraplexes, and other targets. Imidazole-containing compounds that display anticancer activity by unknown/undefined mechanisms are also described, as well as key features of structure-activity relationships. This review is intended to provide an overview of recent advances in imidazole-based anticancer drug discovery and development, as well as inspire the design and synthesis of new anticancer molecules.

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“…Cinnamic acids are natural products known for their wide pharmacological activities [ 60 ]. Employing the pharmacophore-based design approach, a new hybrid 50 was synthesized from imidazole and cinnamic acid and its activity evaluated against lung and breast cancer cell lines [ 61 ]. In addition to inhibiting tubulin polymerization and arresting G2/M phase of the cell cycle, the compound displayed its cytotoxicity against all the cell lines with IC 50 in the range of 0.25 to 1.5 μM [ 61 ].…”

Section: Heterocyclic Compoundsmentioning

confidence: 99%

“…Employing the pharmacophore-based design approach, a new hybrid 50 was synthesized from imidazole and cinnamic acid and its activity evaluated against lung and breast cancer cell lines [ 61 ]. In addition to inhibiting tubulin polymerization and arresting G2/M phase of the cell cycle, the compound displayed its cytotoxicity against all the cell lines with IC 50 in the range of 0.25 to 1.5 μM [ 61 ]. Using a similar approach, Li et al synthesized a series of imidazole derivatives of dehydroabietic acid and found them to exhibit antitumor activities via cell cycle arrest at the S phase, activation of intracellular ROS and decrease in mitochondrion potential leading to apoptosis [ 62 ].…”

Section: Heterocyclic Compoundsmentioning

confidence: 99%

Synthetic and Naturally Occurring Heterocyclic Anticancer Compounds with Multiple Biological Targets

et al. 2021

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Cancer is a complex group of diseases initiated by abnormal cell division with the potential of spreading to other parts of the body. The advancement in the discoveries of omics and bio- and cheminformatics has led to the identification of drugs inhibiting putative targets including vascular endothelial growth factor (VEGF) family receptors, fibroblast growth factors (FGF), platelet derived growth factors (PDGF), epidermal growth factor (EGF), thymidine phosphorylase (TP), and neuropeptide Y4 (NY4), amongst others. Drug resistance, systemic toxicity, and drug ineffectiveness for various cancer chemo-treatments are widespread. Due to this, efficient therapeutic agents targeting two or more of the putative targets in different cancer cells are proposed as cutting edge treatments. Heterocyclic compounds, both synthetic and natural products, have, however, contributed immensely to chemotherapeutics for treatments of various diseases, but little is known about such compounds and their multimodal anticancer properties. A compendium of heterocyclic synthetic and natural product multitarget anticancer compounds, their IC50, and biological targets of inhibition are therefore presented in this review.

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Synthesis and biological evaluation of substituted N-(2-(1H-benzo[d]imidazol-2-yl)phenyl)cinnamides as tubulin polymerization inhibitors

Cited by 32 publications

References 41 publications

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

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

Imidazoles as Potential Anticancer Agents: An Update on Recent Studies

Synthetic and Naturally Occurring Heterocyclic Anticancer Compounds with Multiple Biological Targets

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