Albendazole and Mebendazole as Anti-Parasitic and Anti-Cancer Agents: an Update

Korean Journal of Parasitology, Journal Year: 2021, Volume and Issue: 59(3), P. 189 - 225

Published: June 21, 2021

The use of albendazole and mebendazole, i.e., benzimidazole broad-spectrum anthelmintics, in treatment parasitic infections, as well cancers, is briefly reviewed. These drugs are known to block the microtubule systems parasites mammalian cells leading inhibition glucose uptake transport finally cell death. Eventually they exhibit ovicidal, larvicidal, vermicidal effects on parasites, tumoricidal hosts. Albendazole mebendazole most frequently prescribed for intestinal nematode infections (ascariasis, hookworm trichuriasis, strongyloidiasis, enterobiasis) can also be used tapeworm (taeniases hymenolepiasis). However, these considerable therapeutic against tissue nematode/cestode (visceral, ocular, neural, cutaneous larva migrans, anisakiasis, trichinosis, hepatic capillariasis, angiostrongyliasis, gnathostomiasis, gongylonemiasis, thelaziasis, dracunculiasis, cerebral subcutaneous cysticercosis, echinococcosis). filarial (lymphatic filariasis, onchocerciasis, loiasis, mansonellosis, dirofilariasis) alone or combination with other drugs, such ivermectin diethylcarbamazine. was tried even trematode (fascioliasis, clonorchiasis, opisthorchiasis, fluke infections) protozoan (giardiasis, vaginal trichomoniasis, cryptosporidiosis, microsporidiosis). generally safe few side effects; however, when prolonged time (>14-28 days) only 1 time, liver toxicity reactions may occur. In hookworms, Trichuris trichiura, possibly Ascaris lumbricoides, Wuchereria bancrofti, Giardia sp., there emerging issues drug resistance. It particular note that have been repositioned promising anti-cancer drugs. shown active vitro vivo (animals) liver, lung, ovary, prostate, colorectal, breast, head neck melanoma. Two clinical reports 2 case revealed human patients having variable types cancers. because albendazole, example, neutropenia due myelosuppression, if high doses a currently more popularly than trials.

Language: Английский

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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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Drug repurposing for cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: April 18, 2024

Abstract Cancer, a complex and multifactorial disease, presents significant challenge to global health. Despite advances in surgical, radiotherapeutic immunological approaches, which have improved cancer treatment outcomes, drug therapy continues serve as key therapeutic strategy. However, the clinical efficacy of is often constrained by resistance severe toxic side effects, thus there remains critical need develop novel therapeutics. One promising strategy that has received widespread attention recent years repurposing: identification new applications for existing, clinically approved drugs. Drug repurposing possesses several inherent advantages context since repurposed drugs are typically cost-effective, proven be safe, can significantly expedite development process due their already established safety profiles. In light this, present review offers comprehensive overview various methods employed repurposing, specifically focusing on treat cancer. We describe antitumor properties candidate drugs, discuss detail how they target both hallmarks tumor cells surrounding microenvironment. addition, we examine innovative integrating with nanotechnology enhance topical delivery. also emphasize role play when used part combination regimen. To conclude, outline challenges associated consider future prospects these transitioning into application.

Language: Английский

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Revisiting Activity of Some Nocodazole Analogues as a Potential Anticancer Drugs Using Molecular Docking and DFT Calculations

Frontiers in Chemistry, Journal Year: 2021, Volume and Issue: 9

Published: March 24, 2021

Although potential anticancer activities of benzimidazole-based anthelmintic drugs have been approved by preclinical and clinical studies, modes binding interactions not reported so far. Therefore, in this study, we aimed to propose some anthelmintics with one the most important cancer targets (Tubulin protein). Studied were selected based on their structural similarity cocrystallized ligand (Nocodazole) tubulin protein. Quantum mechanics calculations also employed for characterization electronic configuration studied at atomic molecular level. Order affinities tested benzimidazole toward colchicine site protein is as follows: Flubendazole > Oxfendazole Nocodazole Mebendazole Albendazole Oxibendazole Fenbendazole Ciclobendazole Thiabendazole Bendazole. By analyzing mode hydrogen bond length between nine site, was found bind more efficiently than other derivatives. The quantum studies showed that electron density HOMO together MEP map are quite similar which consistent calculated affinities. Our study has ramifications considering repurposing a promising candidate.

Language: Английский

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Integrating cell morphology with gene expression and chemical structure to aid mitochondrial toxicity detection

Communications Biology, Journal Year: 2022, Volume and Issue: 5(1)

Published: Aug. 23, 2022

Mitochondrial toxicity is an important safety endpoint in drug discovery. Models based solely on chemical structure for predicting mitochondrial are currently limited accuracy and applicability domain to the space of training compounds. In this work, we aimed utilize both -omics data push beyond state-of-the-art. We combined Cell Painting Gene Expression with structural information from Morgan fingerprints 382 perturbants tested Tox21 membrane depolarization assay. observed that toxicants differ non-toxic compounds morphological identified compound clusters having similar mechanisms toxicity, thereby indicating provides biological insights related action endpoint. further showed models combining Painting, features improved model performance external test set 244 by 60% (in terms F1 score) extrapolation new space. The our was comparable dedicated vitro assays toxicity. Our results suggest descriptors readouts enhances detection toxicants, practical implications

Language: Английский

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Computational Repurposing of Benzimidazole Anthelmintic Drugs As Potential Colchicine Binding Site Inhibitors

Future Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 13(19), P. 1623 - 1638

Published: Sept. 10, 2021

Background: Although some benzimidazole-based anthelmintic drugs are found to possess anticancer activity, their modes of binding interactions have not been reported. Methodology: In this study, we aimed investigate the and electronic configurations nine anthelmintics against one well-known cancer targets (tubulin protein). Results: Binding affinities docked benzimidazole into colchicine-binding site were calculated where flubendazole > oxfendazole nocodazole mebendazole. Flubendazole was bind more efficiently with tubulin protein than other drugs. Quantum mechanics studies revealed that electron density HOMO mebendazole together molecular electrostatic potential map closely similar nocodazole. Conclusion: Our study has ramifications for considering repurposing as a promising candidate.

Language: Английский

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Myofibroblast dedifferentiation proceeds via distinct transcriptomic and phenotypic transitions

JCI Insight, Journal Year: 2021, Volume and Issue: 6(6)

Published: Feb. 9, 2021

Myofibroblasts are the major cellular source of collagen, and their accumulation — via differentiation from fibroblasts resistance to apoptosis is a hallmark tissue fibrosis. Clearance myofibroblasts by dedifferentiation restoration sensitivity has potential reverse Prostaglandin E2 (PGE2) mitogens such as FGF2 have each been shown dedifferentiate myofibroblasts, but our knowledge resultant phenotypes neither comprehensively characterized or compared. Here, we show that PGE2 elicited human lung cAMP/PKA, while utilized MEK/ERK. The 2 mediators yielded transitional cells with distinct transcriptomes, promoting inhibiting proliferation survival. gene expression pattern in isolated lungs mice undergoing resolution experimental fibrosis resembled treated vitro. We conclude myofibroblast can proceed programs exemplified treatment FGF2, occurring vivo most closely resembling former.

Language: Английский

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Inhalation delivery of repurposed drugs for lung cancer: Approaches, benefits and challenges

Journal of Controlled Release, Journal Year: 2021, Volume and Issue: 341, P. 1 - 15

Published: Nov. 13, 2021

Language: Английский

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Application of Mesoporous Silica Nanoparticles in Cancer Therapy and Delivery of Repurposed Anthelmintics for Cancer Therapy

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(8), P. 1579 - 1579

Published: July 29, 2022

This review focuses on the biomedical application of mesoporous silica nanoparticles (MSNs), mainly focusing therapeutic MSNs for cancer treatment and specifically overcoming challenges currently available anthelmintics (e.g., low water solubility) as repurposed drugs treatment. MSNs, due to their promising features, such tunable pore size volume, ability control drug release, convert crystalline state an amorphous state, are appropriate carriers delivery with improved solubility hydrophobic drugs. The applications can be further by development MSN-based multimodal anticancer therapeutics photosensitizer-, photothermal-, chemotherapeutics-modified MSNs) chemical modifications, poly ethyleneglycol (PEG)ylation. In this review, various (photodynamic sonodynamic therapies, chemotherapy, radiation therapy, gene immunotherapy) and, in particular, carrier therapy have been discussed. Additionally, issues related safety these deeply According findings literature MSN nanosystems a approach improving efficacy diagnostic chemotherapeutic agents. Moreover, systems seem efficient strategy help decrease costs reducing dose.

Language: Английский

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Repurposing approved non-oncology drugs for cancer therapy: a comprehensive review of mechanisms, efficacy, and clinical prospects

European journal of medical research, Journal Year: 2023, Volume and Issue: 28(1)

Published: Sept. 14, 2023

Abstract Cancer poses a significant global health challenge, with predictions of increasing prevalence in the coming years due to limited prevention, late diagnosis, and inadequate success current therapies. In addition, high cost new anti-cancer drugs creates barriers meeting medical needs cancer patients, especially developing countries. The lengthy costly process novel further hinders drug discovery clinical implementation. Therefore, there has been growing interest repurposing approved for other diseases address urgent need effective treatments. aim this comprehensive review is provide an overview potential non-oncology as therapeutic options treatment. These come from various chemotherapeutic classes, including antimalarials, antibiotics, antivirals, anti-inflammatory drugs, antifungals, have demonstrated antiproliferative, pro-apoptotic, immunomodulatory, antimetastatic properties. A systematic literature was conducted identify relevant studies on therapy. Various electronic databases, such PubMed, Scopus, Google Scholar, were searched using appropriate keywords. Studies focusing potential, mechanisms action, efficacy, prospects repurposed treatment included analysis. highlights promising outcomes Drugs belonging different classes notable antitumor effects, inhibiting cell proliferation, promoting apoptosis, modulating immune response, suppressing metastasis. findings suggest these approaches Repurposing provides strategy addressing accessible diverse their properties, offer avenues Further research trials are warranted explore full optimize use treating types. can significantly expedite identifying treatments improve patient cost-effective manner.

Language: Английский

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