Synthesis of new morpholine-benzimidazole-pyrazole hybrids as tubulin polymerization inhibiting anticancer agents

Sagam, Ravikumar Reddy; Nukala, Satheesh Kumar; Nagavath, Rajkumar; Narsimha, Sirassu; Mohammod, Muqeed; Manchal, Ravinder; Thirukovela, Narasimha Swamy

doi:10.1016/j.molstruc.2022.133692

Cited by 18 publications

(1 citation statement)

References 58 publications

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“…Sagam et al synthesized novel morpholine-benzimidazole-pyrazole hybrids as potential tubulin polymerization inhibitors for cancer treatment [ 42 ]. In vitro antitumor screening against MCF7, PC3, and A549 human cancer cell lines showed that compound 15 had higher activity than the standard CA-4, with IC 50 values of 0.042, 0.61, and 0.76 µM against MCF7, PC3, and A549 cells, respectively.…”

Section: Tubulin Polymerization Inhibitorsmentioning

confidence: 99%

Recent Advances in the Development of Pyrazole Derivatives as Anticancer Agents

Zhang

et al. 2023

IJMS

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Pyrazole derivatives, as a class of heterocyclic compounds, possess unique chemical structures that confer them with a broad spectrum of pharmacological activities. They have been extensively explored for designing potent and selective anticancer agents. In recent years, numerous pyrazole derivatives have been synthesized and evaluated for their anticancer potential against various cancer cell lines. Structure–activity relationship studies have shown that appropriate substitution on different positions of the pyrazole ring can significantly enhance anticancer efficacy and tumor selectivity. It is noteworthy that many pyrazole derivatives have demonstrated multiple mechanisms of anticancer action by interacting with various targets including tubulin, EGFR, CDK, BTK, and DNA. Therefore, this review summarizes the current understanding on the structural features of pyrazole derivatives and their structure-activity relationships with different targets, aiming to facilitate the development of potential pyrazole-based anticancer drugs. We focus on the latest research advances in anticancer activities of pyrazole compounds reported from 2018 to present.

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Section: Tubulin Polymerization Inhibitorsmentioning

confidence: 99%

Recent Advances in the Development of Pyrazole Derivatives as Anticancer Agents

Zhang

et al. 2023

IJMS

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Current scenario of pyrazole hybrids with anti‐breast cancer therapeutic applications

2024

Archiv der Pharmazie

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Breast cancer stands as the leading cause of cancer‐related deaths among women globally, but current therapy is restricted to the serious adverse effects and multidrug resistance, necessitating the exploration of novel, safe, and efficient anti‐breast cancer chemotherapeutic agents. Pyrazoles exhibit excellent potential for utilization as effective anti‐breast cancer agents due to their ability to act on various biological targets. Particularly, pyrazole hybrids demonstrated the advantage of targeting multiple pathways, and some of them, which are exemplified by larotrectinib (pyrazolo[1,5‐a]pyrimidine hybrid), can be applied for breast cancer therapy. Thus, pyrazole hybrids hold great promise as useful therapeutic interventions for breast cancer. The aim of this review is to summarize the current scenario of pyrazole hybrids with in vitro and/or in vivo anti‐breast cancer potential, along with the modes of action and structure–activity relationships, covering articles published from 2020 to the present, to streamline the development of rational, effective and safe anti‐breast cancer candidates.

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Synthesis of Quinoline‐Morpholine‐Coupled 1,2,3‐Triazole Hybrids as In vitro EGFR inhibitors

Mamidala

Bokkala²,

Thirukovela³

et al. 2022

ChemistrySelect

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Herein we described the synthesis of some new quinolinemorpholine coupled 1,2,3-triazole hybrids (6 a-n) from 5chloroquinolin-8-ol using well known reactions like Mannich reaction, O-propargylation, and finally copper (I) catalyzed azide-alkyne cycloaddition (CuAAC). The structures of all newly synthesized hybrids were confirmed by 1 H-NMR, 13 C-NMR, and Mass spectra. All of them were screened for their in vitro cytotoxicity towards three human cancer cell lines including MCF-7, A549 and HepG2 by MTT assay where four compounds (6 c, 6 j, 6 m and 6 n) exhibited more potency than the reference erlotinib against all the three cell lines. In vitro tyrosine kinase EGFR inhibition assay for the same four compounds revealed that 6 m has triple inhibiting power with IC 50 value of 0.14 μM and 6 j has nearly double inhibiting power with IC 50 value of 0.22 μM compared to erlotinib. Molecular docking studies with EGFR have shown that all the above four compounds have more binding energies (À 9.09 kcal/mol to À 9.96 kcal/mol) than that of erlotinib (-7.69 kcal/mol). Finally, in silico pharmacokinetic profile was achieved using SWISS/ADME and pkCSM, where all the four compounds followed Lipinski rule, Veber rule, Egan rule and Muegge rule and the lipophilicity (ClogP) was found to be ranging from 2.98 to 3.69.

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Synthesis of new morpholine-benzimidazole-pyrazole hybrids as tubulin polymerization inhibiting anticancer agents

Cited by 18 publications

References 58 publications

Recent Advances in the Development of Pyrazole Derivatives as Anticancer Agents

Recent Advances in the Development of Pyrazole Derivatives as Anticancer Agents

Current scenario of pyrazole hybrids with anti‐breast cancer therapeutic applications

Synthesis of Quinoline‐Morpholine‐Coupled 1,2,3‐Triazole Hybrids as In vitro EGFR inhibitors

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