Benzimidazole and its derivatives as cancer therapeutics: The potential role from traditional to precision medicine

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 13(2), P. 478 - 497

Published: Sept. 21, 2022

Cancer is the second leading cause of mortality globally which remains a continuing threat to human health today. Drug insensitivity and resistance are critical hurdles in cancer treatment; therefore, development new entities targeting malignant cells considered high priority. Targeted therapy cornerstone precision medicine. The synthesis benzimidazole has garnered attention medicinal chemists biologists due its remarkable pharmacological properties. Benzimidazole heterocyclic pharmacophore, an essential scaffold drug pharmaceutical development. Multiple studies have demonstrated bioactivities derivatives as potential anticancer therapeutics, either through specific molecules or non-gene-specific strategies. This review provides update on mechanism actions various structure‒activity relationship from conventional healthcare bench clinics.

Language: Английский

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The Antitumor Potentials of Benzimidazole Anthelmintics as Repurposing Drugs

Immune Network, Journal Year: 2020, Volume and Issue: 20(4)

Published: Jan. 1, 2020

The development of refractory tumor cells limits therapeutic efficacy in cancer by activating mechanisms that promote cellular proliferation, migration, invasion, metastasis, and survival. Benzimidazole anthelmintics have broad-spectrum action to remove parasites both human veterinary medicine. In addition being antiparasitic agents, benzimidazole are known exert anticancer activities, such as the disruption microtubule polymerization, induction apoptosis, cell cycle (G2/M) arrest, anti-angiogenesis, blockage glucose transport. These antitumorigenic effects even extend resistant approved therapies when combination with conventional therapeutics, enhance hold promise adjuvants. Above all, these may offer a broad, safe spectrum treat cancer, demonstrated their long history use agents. present review summarizes central literature regarding anthelmintics, including albendazole, parbendazole, fenbendazole, mebendazole, oxibendazole, oxfendazole, ricobendazole, flubendazole lines, animal models, clinical trials. This provides valuable information on how improve quality life patients cancers increasing treatment options decreasing side from therapy.

Language: Английский

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Polyploidy formation in cancer cells: How a Trojan horse is born

Seminars in Cancer Biology, Journal Year: 2021, Volume and Issue: 81, P. 24 - 36

Published: March 14, 2021

Ploidy increase has been shown to occur in different type of tumors and participate tumor initiation resistance the treatment. Polyploid giant cancer cells (PGCCs) are with multiple nuclei or a single nucleus containing complete sets chromosomes. The mechanism leading formation PGCCs may depend on: endoreplication, mitotic slippage, cytokinesis failure, cell fusion cannibalism. Polyploidy might be triggered response various genotoxic stresses including: chemotherapeutics, radiation, hypoxia, oxidative stress environmental factors like: air pollution, UV light hyperthermia. A fundamental feature polyploid is generation progeny during reversal state (depolyploidization) that show high aggressiveness resulting resistant disease recurrence. Therefore, we propose modern anti-cancer therapies should designed taking under consideration polyploidization/ depolyploidization processes, which confer polyploidization hidden potential similar Trojan horse delayed aggressiveness. Various mechanisms polyploidy discussed this review.

Language: Английский

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A Therapeutic Journey of Pyridine-based Heterocyclic Compounds as Potent Anticancer Agents: A Review (From 2017 to 2021)

Anti-Cancer Agents in Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 22(15), P. 2775 - 2787

Published: March 25, 2022

Abstract: Pyridine derivatives are the most common and significant heterocyclic compounds, which show their fundamental characteristics to various pharmaceutical agents natural products. possess several pharmacological properties a broad degree of structural diversity that is valuable for exploring novel therapeutic agents. These compounds have an extensive range biological activities such as antifungal, antibacterial, anticancer, anti-obesity, anti-inflammatory, antitubercular, antihypertensive, antineuropathic, antihistaminic, antiviral activities, antiparasitic. The potent pyridine allow medicinal chemists synthesize effective chemotherapeutic Consequently, imperative objective this comprehensive review summarize investigate literature regarding recent advancements in pyridine-based heterocycles treat kinds cancer. Furthermore, performances were compared with some standard drugs, including etoposide, sorafenib, cisplatin, triclosan, against different cancer cell lines. We hope study will support new thoughts pursue active less toxic rational designs.

Language: Английский

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Repurposing of Benzimidazole Anthelmintic Drugs as Cancer Therapeutics

Cancers, Journal Year: 2022, Volume and Issue: 14(19), P. 4601 - 4601

Published: Sept. 22, 2022

Benzimidazoles have shown significant promise for repurposing as a cancer therapy. The aims of this review are to investigate the possibilities and limitations anti-cancer effects benzimidazole anthelmintics suggest ways overcome these limitations. This included studies on 11 benzimidazoles. Largely divided into three parts, i.e., preclinical effects, clinical pharmacokinetic properties, we examine characteristics each attempt elucidate its key properties. Although many demonstrated benzimidazoles, there is limited evidence regarding their in settings. might be because trials conducted using benzimidazoles failed restrict participants with specific criteria including entities, stages, genetic participants. In addition, drugs low bioavailability, which results insufficient plasma concentration levels. Additional whole pathways development strategies, formulations, could result enhancements situations.

Language: Английский

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Resveratrol Derivative Exhibits Marked Antiproliferative Actions, Affecting Stemness in Pancreatic Cancer Cells

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 1977 - 1977

Published: Jan. 19, 2023

Pancreatic cancer (PC) is one of the deadliest malignancies, with an increasing incidence and limited response to current therapeutic options. Therefore, more effective low-toxic agents are needed improve PC patients' outcomes. Resveratrol (RSV) a natural polyphenol multiple biological properties, including anticancer effects. In this study, we explored antiproliferative activities newly synthetized RSV analogues in panel cell lines evaluated physicochemical properties most active compound. This derivative exhibited marked effects cells through mechanisms involving DNA damage, apoptosis induction, interference cycle progression, as assessed using flow cytometry immunoblot analysis proteins, PARP cleavage, H2AX phosphorylation. Notably, compound induced consistent reduction subpopulation CD133+EpCAM+ stem-like phenotype, paralleled by dramatic on clonogenicity. Moreover, had negligible toxicity against normal HFF-1 and, thus, good selectivity index values toward lines. Remarkably, its higher lipophilicity stability human plasma, compared RSV, might ensure better permeation along gastrointestinal tract. Our results provide insights into action contributing activity synthetic analogue, supporting potential value search for safe treatment.

Language: Английский

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Current trends and future prospects of drug repositioning in gastrointestinal oncology

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 4, 2024

Gastrointestinal (GI) cancers comprise a significant number of cancer cases worldwide and contribute to high percentage cancer-related deaths. To improve survival rates GI patients, it is important find implement more effective therapeutic strategies with better prognoses fewer side effects. The development new drugs can be lengthy expensive process, often involving clinical trials that may fail in the early stages. One strategy address these challenges drug repurposing (DR). Drug developmental involves using existing approved for other diseases leveraging their safety pharmacological data explore potential use treating different diseases. In this paper, we outline associated DR as promising alternative approach. We have presented an extensive review methodologies, research efforts examples repurposed within various types, such colorectal, pancreatic liver cancers. Our aim provide comprehensive overview employing approach inform future endeavors field.

Language: Английский

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Screening of Benzimidazole-Based Anthelmintics and Their Enantiomers as Repurposed Drug Candidates in Cancer Therapy

Pharmaceuticals, Journal Year: 2021, Volume and Issue: 14(4), P. 372 - 372

Published: April 17, 2021

Repurposing of approved non-antitumor drugs represents a promising and affordable strategy that may help to increase the repertoire effective anticancer drugs. Benzimidazole-based anthelmintics are antiparasitic commonly employed both in human veterinary medicine. Benzimidazole compounds being considered for drug repurposing due antitumor activities displayed by some members family. In this study, we explored effects large series benzimidazole-based (and enantiomerically pure forms those containing stereogenic center) on viability different tumor cell lines derived from paraganglioma, pancreatic colorectal cancer. Flubendazole, parbendazole, oxibendazole, mebendazole, albendazole fenbendazole showed most consistent antiproliferative effects, displaying IC50 values low micromolar range, or even nanomolar range. silico evaluation their physicochemical, pharmacokinetics medicinal chemistry properties also provided useful information related chemical structures potential these compounds. Furthermore, view cancer therapy considering pharmaceutically active have mechanisms action, performed an target prediction assess polypharmacology benzimidazoles, which highlighted previously unknown cancer-relevant molecular targets.

Language: Английский

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Drug Repurposing, an Attractive Strategy in Pancreatic Cancer Treatment: Preclinical and Clinical Updates

Cancers, Journal Year: 2021, Volume and Issue: 13(16), P. 3946 - 3946

Published: Aug. 5, 2021

Pancreatic cancer (PC) is one of the deadliest malignancies worldwide, since patients rarely display symptoms until an advanced and unresectable stage disease. Current chemotherapy options are unsatisfactory there urgent need for more effective less toxic drugs to improve dismal PC therapy. Repurposing non-oncology in treatment represents a very promising therapeutic option different compounds currently being considered as candidates repurposing this tumor. In review, we provide update on some most FDA-approved, non-oncology, repurposed drug that show prominent clinical preclinical data pancreatic cancer. We also focus proposed mechanisms action known molecular targets they modulate PC. Furthermore, explorative bioinformatic analysis, which suggests have additional, unexplored, oncology-relevant targets. Finally, discuss recent developments regarding immunomodulatory role displayed by these drugs, may expand their potential application synergy with approved anticancer agents mostly ineffective single

Language: Английский

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Therapeutic Efficacy of Benzimidazole and Its Analogs: An Update

Polycyclic aromatic compounds, Journal Year: 2022, Volume and Issue: 43(7), P. 6549 - 6569

Published: Sept. 6, 2022

Benzimidazoles, one of the nitrogen heterocycles, possess pharmaceutical and biological potential. This heterocycle has been known for pharmacological activities such as antifungal, antibacterial, antiparasitic. The reports on compounds containing this basic moiety are well-reported in literature, specifically anthelmintic proton pump inhibitors. review covers synthesis benzimidazole analogs by feasible methods from our laboratory. Also, present explores recent designed anticancer, antiviral agents.

Language: Английский

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