New imidazole derivatives of 2(3<i>H</i>)‐benzazolones as potential antifungal agents

Petrov, Ognyan; Gerova, Mariana; Petrova, Katya V.; Ivanova, Yordanka

doi:10.1002/jhet.11

Cited by 11 publications

(11 citation statements)

References 13 publications

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“…While the MIC value of 4‐chloride 102b (MIC = 0.5 μg/mL) toward C. albicans was fourfold lower than that of fluconazole (MIC = 2 μg/mL). However, replacement of diphenyl group in bifonazole by benzoxazolone ring ( 103 ) led to completely lost anti‐ Candida efficacy . The high antifungal potency of 102a ‐ b might be attributed to their small size, which made them convenient to penetrate into fungi cell, and the chlorine atoms with a positive effect was helpful for improving affinity toward the heme binding site …”

Section: Imidazoles As Antifungal Agentsmentioning

confidence: 99%

Comprehensive Review in Current Developments of Imidazole-Based Medicinal Chemistry

et al. 2013

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Imidazole ring is an important five-membered aromatic heterocycle widely present in natural products and synthetic molecules. The unique structural feature of imidazole ring with desirable electron-rich characteristic is beneficial for imidazole derivatives to readily bind with a variety of enzymes and receptors in biological systems through diverse weak interactions, thereby exhibiting broad bioactivities. The related research and developments of imidazole-based medicinal chemistry have become a rapidly developing and increasingly active topic. Particularly, numerous imidazole-based compounds as clinical drugs have been extensively used in the clinic to treat various types of diseases with high therapeutic potency, which have shown the enormous development value. This work systematically gives a comprehensive review in current developments of imidazole-based compounds in the whole range of medicinal chemistry as anticancer, antifungal, antibacterial, antitubercular, anti-inflammatory, antineuropathic, antihypertensive, antihistaminic, antiparasitic, antiobesity, antiviral, and other medicinal agents, together with their potential applications in diagnostics and pathology. It is hoped that this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic imidazole-based medicinal drugs, as well as more effective diagnostic agents and pathologic probes.

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Section: Imidazoles As Antifungal Agentsmentioning

confidence: 99%

Comprehensive Review in Current Developments of Imidazole-Based Medicinal Chemistry

et al. 2013

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Section: Introductionmentioning

confidence: 99%

“…Among azoles, imidazole and triazole analogues are present in many effective antifungal drugs widely used for the treatment of topical or inner mycoses, in particular AIDS-related mycotic pathologies [4]. The main effect of antifungal azoles is to block fungal ergosterol biosynthesis by preventing the access of the natural substrate lanosterol to the active site of the cytochrome P-450-dependent enzyme 14α-lanosterol demethylase [4,5]. Over the past couple of decades, a number of antifungal imidazole agents were discovered and introduced in clinical practice such as clotrimazole, bifonazole and miconazole, whereas fluconazole was identified as one of the most important antifungal drugs in the triazole family [6].…”

Section: Introductionmentioning

confidence: 99%

Regioselective synthesis and antimicrobial studies of novel bridgehead nitrogen heterocycles containing the thienopyrimidinone skeleton

Gaber

Moussa

2011

Eur. J. Chem.

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KEYWORDSVersatile 2-(alkylthio)pyrimidine-type and 2-(phenacylamino)thiophene building blocks (4ad) and 16 were obtained based on an ortho functionalized thiophene derivative 1. A novel series of thieno[2,3-d]pyrimidin-4-one derivatives with annelated bridgehead nitrogen heterocycles was synthesized starting from precursors 4 and 16 through convenient methods. Cyclocondensation of 2-(phenacylthio)pyrimidinone derivative (4b) with sulfuric acid led to the tricyclic thiazole derivative 5. Initial hydrazinolysis of 3-(carbethoxymethyl)pyrimidinone derivative (4d) followed by nitrous acid deamination of the formed N-aminolactam (7) to obtain a N-protodeamino analogue 8a, which on further treatment with formaldehyde and piperidine yielded the respective Mannich-type base 8b. On the other hand, initial hydrazinolysis of 3-unsubstituted pyrimidinone derivative 4a and subsequent acetylation gave the condensed 3-methyltriazole derivative 12, whereas the condensed pyrrole derivative 19 was obtained by heterocyclization of 2-phenacylamine derivative 16 with malononitrile. All newly-obtained thienopyrimidinones with annelated bridgehead nitrogen were screened for their antimicrobial activity against strains of a representative panel of Gram-positive and Gram-negative bacteria as well as fungi together with reference drugs. The compounds under investigation displayed generally good in vitro antibacterial and antifungal activities, with compound 8b that has a N-piperidinylmethyl moiety showing essentially the highest inhibition in both assays. Despite promising antimicrobial activity of N-1-substituted imidazole derivative 8b, the corresponding N-1-unsubstituted analogue 8a displayed poor activity. The heteroannelation of a N-(piperidinylmethyl)imidazole or 3-methyltriazole moiety to the thienopyrimidinone scaffold could be considered as a potential strategy for the development of new therapeutic antimicrobial agents.Thienopyrimidinone Alkylation Cyclodehydration Hydrazinolysis Acetylation Antimicrobial activity

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“…Fungal infections, mostly caused by Candida albicans, are often aggravated through the widespread use of broad-spectrum antibiotics, immunosuppressive agents, anticancer and anti-AIDS drugs [1,2]. Despite advances in antimicrobial therapy, many problems remain to be solved for a new generation of antimicrobial agents.…”

Section: Introductionmentioning

confidence: 99%

“…Despite advances in antimicrobial therapy, many problems remain to be solved for a new generation of antimicrobial agents. The main problem in the treatment of microbial infections is the increasing prevalence of drug resistance especially in patients chronically subjected to antimycotic therapy such as persons infected with HIV [2,3]. Therefore, the development of new and efficacious antimicrobial drugs is a very important goal, and most of the research efforts in this field are directed towards the design of new agents.…”

Section: Introductionmentioning

confidence: 99%

Regioselective synthesis and biological evaluation of some novel thiophene-containing heterocyclic scaffolds as potential chemotherapeutic agents

Gaber

Bagley

2011

Eur. J. Chem.

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KEYWORDSIn the reaction of 2-amino-3-carbethoxythiophene derivative 2b with hydrazine hydrate the respective aminocarbohydrazide 3 was isolated. Treatment of the latter product with carbon disulfide in alkaline medium caused a heterocyclization to give 1,3,4-oxadiazole-2-thione 5 rather than 3-amino-2-thioxothieno[2,3-d]pyrimidin-4-one 4, which could be obtained on treatment of carbohydrazide 3 with thiourea. The structure of products 4 and 5 was proved by spectroscopic methods and chemical transformations. Derivatization led to two novel series of condensed and uncondensed thiophenes, which were of significant interest for biological study. Since compound 4 contains two adjacent reactive functional groups, it reacted readily with different electrophilic reagents to provide a series of thieno[2,3-d]pyrimidin-4-one derivatives with annelated bridgehead nitrogen heterocycles 8-11, whereas a second series of 3-heteroaryl-substituted thiophenes 13-17 was obtained by thioamide functionalization in 1,3,4-oxadiazole derivative 5 using various chemical reagents. The new thiophene-based derivatives were evaluated for their preliminary antimicrobial activity against a representative panel of Gram-positive and Gram-negative bacteria as well as fungi strains. The compounds tested displayed different levels of inhibitory effects, with the assays carried out on two pathogenic bacteria and two pathogenic fungi. Of these compounds, the monocyclic aminothiophene derivative 15 showed the highest effect on pathogenic bacteria, while the tricyclic condensed thiophene derivative 8 was observed to have the same inhibitory effect against pathogenic mould (Aspergillus flavus) as the reference drug Amphotericin B. For those derivatives belonging to first series of condensed thiophenes with annelated bridgehead nitrogen heterocycles, it has been observed that the antibacterial effect was in general found to be significantly higher than the corresponding uncondensed analogues. Although most of the condensed and uncondensed thiophenes under investigation showed generally remarkable in vitro antibacterial activity, unfortunately, no significant antifungal activity was observed with any of the compounds tested except for 8. Surprisingly, compound 8 displayed an excellent effect on fungus (A. flavus) on the one hand, whereas the lowest effect on bacteria on the other. The attachment of a triazolothiadiazine moiety to a thiophene ring could be considered as a promising strategy for the development of new therapeutic antibacterial agents related to the aminothiophene system. Thienopyrimidinone Cyclocondensation Cyclodesulfurization Hydrazinolysis Alkylation Antimicrobial activity

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New imidazole derivatives of 2(3H)‐benzazolones as potential antifungal agents

Cited by 11 publications

References 13 publications

Comprehensive Review in Current Developments of Imidazole-Based Medicinal Chemistry

Comprehensive Review in Current Developments of Imidazole-Based Medicinal Chemistry

Regioselective synthesis and antimicrobial studies of novel bridgehead nitrogen heterocycles containing the thienopyrimidinone skeleton

Regioselective synthesis and biological evaluation of some novel thiophene-containing heterocyclic scaffolds as potential chemotherapeutic agents

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