Antibacterial and antifungal activities of benzimidazole and benzoxazole derivatives

Elnima, E I; Zubair, Mohammad; Al-Badr, Abdullah A.

doi:10.1128/aac.19.1.29

Cited by 75 publications

(30 citation statements)

References 4 publications

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“…However, in medicine they are not used for treatment of fungal infections but rather as antihelminthics (mebendazole, eskazole). Many other derivatives have previously been described to have antifungal activities (12,39). In addition, an antineoplastic activity of certain benzimidazoles, like nocodazole, has been identified, pointing to a certain level of cytotoxic effects.…”

Section: Discussionmentioning

confidence: 99%

A Screening Assay Based on Host-Pathogen Interaction Models Identifies a Set of Novel Antifungal Benzimidazole Derivatives

Burger‐Kentischer

Finkelmeier

Keller

et al. 2011

Antimicrob Agents Chemother

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Fungal infections are a serious health problem in clinics, especially in the immune-compromised patient. Disease ranges from widespread superficial infections like vulvovaginal infections to life-threatening systemic candidiasis. Especially for systemic mycoses, only a limited arsenal of antifungals is available. The most commonly used classes of antifungal compounds used include azoles, polyenes, and echinocandins. Due to emerging resistance to standard therapy, significant side effects, and high costs for several antifungals, there is a medical need for new antifungals in the clinic and general practice. In order to expand the arsenal of compounds with antifungal activities, we screened a compound library including more than 35,000 individual compounds derived from organic synthesis as well as combinatorial compound collections representing mixtures of compounds for antimycotic activity. In total, more than 100,000 compounds were screened using a new type of activity-selectivity assay, analyzing both the antifungal activity and the compatibility with human cells at the same time. One promising hit, an (S)-2-aminoalkyl benzimidazole derivative, was developed among a series of lead compounds showing potent antifungal activity. (S)-2-(1-Aminoisobutyl)-1-(3-chlorobenzyl) benzimidazole showed the highest antifungal activity and the best compatibility with human cells in several cell culture models and against a number of clinical isolates of several species of pathogenic Candida yeasts. Transcriptional profiling indicates that the newly discovered compound is a potential inhibitor of the ergosterol pathway, in contrast to other benzimidazole derivatives, which target microtubules.

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Section: Discussionmentioning

confidence: 99%

A Screening Assay Based on Host-Pathogen Interaction Models Identifies a Set of Novel Antifungal Benzimidazole Derivatives

Burger‐Kentischer

Finkelmeier

Keller

et al. 2011

Antimicrob Agents Chemother

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“…They are used against several systemic parasitoses including nematodoses, hydatidosis, taeniasis, and others (Campbell, 1990). They are also active against various protozoa (Katiyar et al, 1994) and Grampositive bacteria (Elnima et al, 1981). ABZ is used to treat microsporidial and cryptosporidial infections, which can cause lethal diarrhea in patients treated with immunosuppressive drugs or those infected with HIV (Zulu et al, 2002;Didier et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Transport of Anthelmintic Benzimidazole Drugs by Breast Cancer Resistance Protein (Bcrp/Abcg2)

Merino¹,

Jonker²,

Wagenaar³

et al. 2005

Drug Metab Dispos

114

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ABSTRACT:Methylcarbamate benzimidazoles [albendazole (ABZ), fenbendazole (FBZ), and their respective sulfoxide derivatives, albendazole sulfoxide (ABZSO) and oxfendazole (OXF)] are therapeutically important anthelmintic agents with low bioavailability. We studied their in vitro interaction with the apical ATP-binding cassette (ABC) drug efflux transporters, breast cancer resistance protein (BCRP/ ABCG2), P-glycoprotein (ABCB1), and MRP2 (ABCC2) using MD-CKII cells transduced with human MDR1, MRP2, and BCRP, and murine Bcrp1 cDNAs. These ABC drug efflux transporters extrude a wide range of xenotoxins from cells in intestine, liver, and other organs, thus affecting the bioavailability of many compounds. In transport experiments, ABZSO and OXF were transported efficiently by murine Bcrp1 and moderately by human BCRP, but not by MDR1 or MRP2. ABZ and FBZ were not found to be Bcrp1, MRP2, or P-glycoprotein substrates in vitro. OXF was found to be a good BCRP/Bcrp1 inhibitor, with somewhat higher potency in the MDCKII-BCRP cell line. The latter results were confirmed by flow cytometry experiments demonstrating inhibition by OXF of murine Bcrp1-and human BCRP-mediated mitoxantrone transport. Further studies of interactions between OXF and known BCRP/Bcrp1 substrates will be of interest. The use of efficacious BCRP/Bcrp1 inhibitors might increase the extent and duration of systemic exposure to ABZSO and OXF, with possible therapeutically beneficial effects in extra-intestinal infections.Albendazole (ABZ), fenbendazole (FBZ), and their sulfoxide derivatives (albendazole sulfoxide/ricobendazole, ABZSO; and fenbendazole-sulfoxide/oxfendazole, OXF) are methylcarbamate benzimidazoles with a broad-spectrum anthelmintic activity, widely used in human and veterinary medicine. They are used against several systemic parasitoses including nematodoses, hydatidosis, taeniasis, and others (Campbell, 1990). They are also active against various protozoa (Katiyar et al., 1994) and Grampositive bacteria (Elnima et al., 1981). ABZ is used to treat microsporidial and cryptosporidial infections, which can cause lethal diarrhea in patients treated with immunosuppressive drugs or those infected with HIV (Zulu et al., 2002;Didier et al., 2004). In addition, ABZ has shown antitumor activity (Morris et al., 2001;Pourgholami et al., 2004). Both sulfoxide derivatives (ABZSO and OXF) are the main active metabolites found in plasma after oral administration of the parent compounds, ABZ and FBZ (Lanusse and Prichard, 1993), but they are also available as commercial formulations themselves.Especially FBZ, but also ABZ, and their sulfoxides are poorly absorbed from the gastrointestinal tract (Lanusse and Prichard, 1993;Lanusse et al., 1995;Capece et al., 2000). For treatment of intestinal luminal parasites, this is ideal: intestinal concentration of the drug remains high, and there is little risk of systemic toxicity. However, for systemic treatments elsewhere in the body, substantial (systemic) uptake of the drugs is needed, and low benzimidazole bio...

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“…The in vitro antibacterial and antifungal activities of six benzimidazole and benzoxazole derivatives (15) were tested on clinical isolates where two of the benzoxazoles were found to be active [5]. Some 2-(N-Aryl-carboxamidomethylthio)benzoxazoles (16) and corresponding sulfones (17) were prepared, and their antimicrobial activity was assayed against some bacteria and fungi and was found to exhibit 20-70% inhibition at a concentration of 0.1 mg/ml [6].…”

Section: Jyothi and Merugumentioning

confidence: 99%

An Update on the Synthesis of Benzoxazoles

Jyothi

Merugu

2017

Asian J Pharm Clin Res

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Benzoxazoles being structurally similar to bases adenine and guanine interact with biomolecules present in living systems. These compounds possess antimicrobial, central nervous system activities, antihyperglycemic potentiating activity, analgesic, and anti-inflammatory activity. It can also be used as starting material for other bioactive molecules. Modifications in structure and the biological profiles of new generations of benzoxazoles were found to be more potent with enhanced biological activity. Considering all these, we have prepared this review and discussed the synthesis and biological activities of benzoxazoles.

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Antibacterial and antifungal activities of benzimidazole and benzoxazole derivatives

Cited by 75 publications

References 4 publications

A Screening Assay Based on Host-Pathogen Interaction Models Identifies a Set of Novel Antifungal Benzimidazole Derivatives

A Screening Assay Based on Host-Pathogen Interaction Models Identifies a Set of Novel Antifungal Benzimidazole Derivatives

Transport of Anthelmintic Benzimidazole Drugs by Breast Cancer Resistance Protein (Bcrp/Abcg2)

An Update on the Synthesis of Benzoxazoles

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