Identification of new benzimidazole-triazole hybrids as anticancer agents: multi-target recognition,
            <i>in vitro</i>
            and
            <i>in silico</i>
            studies

Othman, Dina I. A.; Hamdi, Abdelrahman; Tawfik, Samar S.; Elgazar, Abdullah A.; Mostafa, Amany S.

doi:10.1080/14756366.2023.2166037

Cited by 29 publications

(19 citation statements)

References 53 publications

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“…ADMET prediction has been extensively used to obtain insights about the pharmacokinetic properties of drug-like compounds. , In the case of compound 5b , both predicted values in the PkCSM server and PreADMET showed that human intestinal absorption was 100 and 97.83%, respectively. The compounds showed a reasonable volume of distribution and skin permeability.…”

Section: Resultsmentioning

confidence: 99%

3-Acetyl-11-keto-β-boswellic Acid-Based Hybrids Alleviate Acetaminophen-Induced Hepatotoxicity in HepG2 by the Regulation of Inflammatory and Oxidative Stress Pathways: An Integrated Approach

Elgazar,

El-Domany,

Eldehna

et al. 2023

ACS Omega

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In an effort to develop new compounds for managing drug-induced liver injury, we prepared 23 novel hybrids based on 3-acetyl-11-keto-β-boswellic acid (AKBA) using various biocompatible linkers. A bioguided approach was employed to identify the most promising hybrid. Eight compounds exhibited superior anti-inflammatory activity compared to the parent compound. Two of these hybrids (5b and 18) were able to reduce gene expression of TNF-α in LPS-induced inflammation in RAW 264.7 cells, similar to dexamethasone. Subsequently, the hepatoprotective potential of these hybrids was evaluated against acetaminophen (APAP) toxicity in HepG2 cells at doses of 1 and 10 μM. Both hybrids effectively restored cytokine levels, which had been elevated by APAP, to normal levels. Furthermore, they normalized depleted superoxide dismutase and reduced glutathione levels while significantly reducing malondialdehyde (MDA) levels. Network pharmacology analysis suggested that AKBA-based hybrids exert their action by regulating PI3K and EGFR pathways, activating anti-inflammatory mechanisms, and initiating tissue repair and regeneration. Molecular docking studies provided insights into the interaction of the hybrids with PI3K. Additionally, the hybrids demonstrated good stability at different pH levels, following first-order kinetics, with relatively long half-lives, suggesting potential for absorption into circulation without significant degradation.

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Section: Resultsmentioning

confidence: 99%

3-Acetyl-11-keto-β-boswellic Acid-Based Hybrids Alleviate Acetaminophen-Induced Hepatotoxicity in HepG2 by the Regulation of Inflammatory and Oxidative Stress Pathways: An Integrated Approach

Elgazar,

El-Domany,

Eldehna

et al. 2023

ACS Omega

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“…A weak inhibitory effect was observed for Topo II and moderate inhibition for VEGFR‐2 and EGFR for compound 24 . Molecular docking and physicochemical investigations were carried out to shed light on the possible mechanisms of action of the active compounds, as well as DNA binding assays, apoptotic induction studies, cell cycle assessment, physicochemical studies, and apoptotic induction assays [55] …”

Section: Patent Reviewmentioning

confidence: 99%

“…Molecular docking and physicochemical investigations were carried out to shed light on the possible mechanisms of action of the active compounds, as well as DNA binding assays, apoptotic induction studies, cell cycle assessment, physicochemical studies, and apoptotic induction assays. [55] A large number of biologically active components must be combined with a central structure to offer potential anticancer properties. Benzimidazole molecules with triazole groups were deliberately designed as promising cancer inhibitors by Rao and colleagues in this study.…”

Section: University Of California Us10562886b2mentioning

confidence: 99%

Synthesis and Pharmacological Properties of the Benzimidazole Scaffold: A Patent Review

Mehra,

Sangwan

2023

ChemistrySelect

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Benzimidazole derivatives were first discovered in the late 19th and early 20th centuries, marking a significant milestone in the field of chemistry. These compounds have since played a pivotal role in pharmacology, demonstrating a wide array of pharmacological properties that have had a profound impact on medicine and healthcare. The significance of benzimidazole derivatives in pharmacology is undeniable. These compounds have been extensively studied and developed for their diverse and valuable properties. They exhibit potent anticancer activity, with some derivatives displaying the ability to hinder the growth of cancer cells, offering hope in the fight against this disease. Furthermore, benzimidazole derivatives have been involved in the management of cardiovascular conditions as antihypertensive agents, aiding in the control of high blood pressure. Their potential as antidiabetic agents, by influencing glucose metabolism and insulin secretion, holds promise in diabetes treatment. The recent patent literature has focused on structural modifications to the benzimidazole core to expand the arsenal of effective drugs. This review takes a disease‐centric perspective on patented benzimidazoles from 2016 to 2023. The relevant granted patent applications were located using patent databases, USPTO, Google Patents, EPO, WIPO, Lens and Espacenet.

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“…Othman et al 70 developed two new series of benzimidazole-triazole hybrids 6a – h and 7a – g as multi-target inhibitors of EGFR, VEGFR-2, and Topo II (Figure 7 ). The compounds were tested for their anticancer activity and compounds 5a and 6g showed the highest potency against four cancer cell lines: HepG-2, HCT-116, MCF-7, and HeLa.…”

Section: Biological Activity Of Benzimidazole Derivativesmentioning

confidence: 99%

A Review on Benzimidazole Heterocyclic Compounds: Synthesis and Their Medicinal Activity Applications

Alheety,

Mohammed,

Farhan

et al. 2023

SynOpen

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Benzimidazole is a heterocyclic compound formed by fusing the benzene ring with an imidazole ring that contains two nitrogen atoms. Benzimidazole and its derivatives are prepared in different ways, including condensation of o-phenylenediamine with carbonyl compounds (aldehydes and ketones) or with carboxylic acids and their derivatives. The benzimidazoles can also be prepared by rearranging other heterocyclic compounds such as quinoxaline derivatives, triazole derivatives, etc. In recent decades, benzimidazoles were prepared using green methods such as microwaves, ultrasound, and the use of an environmentally friendly catalyst, as well as photochemical reactions. Benzimidazoles have attracted the interest of scientists and researchers due to the great medical efficacy shown by them for various diseases. The benzimidazole derivatives show many pharmacological activities such as anticancer, anti-inflammatory, antioxidant, anticoagulant, antiviral, etc. This review focuses on shedding light on benzimidazole and its derivatives, the most important methods used to prepare it, as well as the biological applications in our daily lives.

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Identification of new benzimidazole-triazole hybrids as anticancer agents: multi-target recognition, in vitro and in silico studies

Cited by 29 publications

References 53 publications

3-Acetyl-11-keto-β-boswellic Acid-Based Hybrids Alleviate Acetaminophen-Induced Hepatotoxicity in HepG2 by the Regulation of Inflammatory and Oxidative Stress Pathways: An Integrated Approach

3-Acetyl-11-keto-β-boswellic Acid-Based Hybrids Alleviate Acetaminophen-Induced Hepatotoxicity in HepG2 by the Regulation of Inflammatory and Oxidative Stress Pathways: An Integrated Approach

Synthesis and Pharmacological Properties of the Benzimidazole Scaffold: A Patent Review

A Review on Benzimidazole Heterocyclic Compounds: Synthesis and Their Medicinal Activity Applications

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