Novel aminopyrimidinyl benzimidazoles as potentially antimicrobial agents: Design, synthesis and biological evaluation

Liu, Hanbo; Gao, Wei‐Wei; Tangadanchu, Vijai Kumar Reddy; Geng, Rong‐Xia

doi:10.1016/j.ejmech.2017.11.027

Cited by 119 publications

(39 citation statements)

References 62 publications

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“…MMV021013 is a 2-pyridyl-4-aminopyrimidine. Antifungal activity has been described for some aminopyrimidines, including 4-(2-Fluorophenyl)-6-trifluoromethyl-2-aminopyrimidine, active against Botrytis cinera [31], and 4-(1H-benzo[d]imidazol-2-yl)-6-(p-tolyl)pyrimidin-2-amine, active against Aspergillus flavus , Candida utilis , and Saccharomyces cerevisiae [32]. The Pathogen Box® classifies this compound as a tuberculosis targeted drug.…”

Section: Discussionmentioning

confidence: 99%

A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis

Coelho

Joffe

Alves

et al. 2020

Preprint

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AbstractChromoblastomycosis (CBM) is a chronic subcutaneous mycosis caused by traumatic implantation of many species of black fungi. Due to the refractoriness of some cases and common recurrence of CBM, a more effective and less time-consuming treatment is mandatory. The aim of this study was to identify compounds with in vitro antifungal activity in the Pathogen Box® compound collection against different CBM agents. Synergism of these compounds with drugs currently used to treat CBM was also assessed. An initial screening of the drugs present in this collection at 1μM was performed with a Fonsecaea pedrosoi clinical strain according to the EUCAST protocol. The compounds with activity against this fungus were also tested against other seven etiologic agents of CBM (Cladophialophora carrionii, Phialophora verrucosa, Exophiala jeanselmei, Exophiala dermatitidis, Fonsecaea monophora, Fonsecaea nubica, and Rhinocladiella similis) at concentrations ranging from 0.039 to 10 μM. The analysis of potential synergism of these compounds with itraconazole and terbinafine was performed by the checkerboard method. Eight compounds inhibited more than 60% of the F. pedrosoi growth: difenoconazole, bitertanol, iodoquinol, azoxytrobin, MMV688179, MMV021013, trifloxystrobin, and auranofin. Iodoquinol produced the lowest MIC values (1.25 - 2.5μM) and MMV688179 showed MICs that were higher than all compounds tested (5 - >10μM). When auranofin and itraconazole were tested in combination, a synergistic interaction (FICI = 0.37) was observed against the C. carrionii isolate. In summary, auranofin, iodoquinol, and MMV021013 were identified as promising compounds to be tested in CBM models of infection.

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Section: Discussionmentioning

confidence: 99%

A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis

Coelho

Joffe

Alves

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…MMV021013 is a 2-pyridyl-4-aminopyrimidine. Antifungal activity has been described for some aminopyrimidines, including4-(2-Fluorophenyl)-6-trifluoromethyl-2-aminopyrimidine, active against Botrytis cinera [40], and 4-(1H-benzo[d]imidazol-2-yl)-6-(p-tolyl)pyrimidin-2-amine, active against Aspergillus flavus, Candida utilis, and Saccharomyces cerevisiae [41]. The Pathogen Box1 classifies this compound as a tuberculosis targeted drug.…”

Section: Plos Onementioning

confidence: 99%

A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis

et al. 2020

View full text Add to dashboard Cite

Chromoblastomycosis (CBM) is a chronic subcutaneous mycosis caused by traumatic implantation of many species of black fungi. Due to the refractoriness of some cases and common recurrence of CBM, a more effective and less time-consuming treatment is mandatory. The aim of this study was to identify compounds with in vitro antifungal activity in the Pathogen Box® compound collection against different CBM agents. Synergism of these compounds with drugs currently used to treat CBM was also assessed. An initial screening of the drugs present in this collection at 1 μM was performed with a Fonsecaea pedrosoi clinical strain according to the EUCAST protocol. The compounds with activity against this fungus were also tested against other seven etiologic agents of CBM (Cladophialophora carrionii, Phialophora verrucosa, Exophiala jeanselmei, Exophiala dermatitidis, Fonsecaea monophora, Fonsecaea nubica, and Rhinocladiella similis) at concentrations ranging from 0.039 to 10 μM. The analysis of potential synergism of these compounds with itraconazole and terbinafine was performed by the checkerboard method. Eight compounds inhibited more than 60% of the F. pedrosoi growth: difenoconazole, bitertanol, iodoquinol, azoxystrobin, MMV688179, MMV021013, trifloxystrobin, and auranofin. Iodoquinol produced the lowest MIC values (1.25-2.5 μM) and MMV688179 showed MICs that were higher than all compounds tested (5->10 μM). When auranofin and itraconazole were tested in combination, a synergistic interaction (FICI = 0.37) was observed against the C. carrionii isolate. Toxicity analysis revealed that MMV021013 showed high selectivity indices (SI � 10) against the fungi tested. In summary, auranofin, iodoquinol, and MMV021013 were identified as promising compounds to be tested in CBM models of infection.

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“…Benzimidazole is yet another nitrogen heterocyclic compound with fused benzene and imidazole rings. It exhibits wide spread biological activities such as antimicrobial [20], antihistaminic [21], antiparasitic [22], antiallergic [23], anticancer [24] and antioxidant [25]. In addition, its derivatives display efficiency in material science field.…”

Section: Revised Manuscript Received On December 15 2019mentioning

confidence: 99%

Novel Benzimidazole Bejeweled Pyrazole: Synthesis, Characterization and Density Functional Theory Analysis

Sivaramakarthikeyan¹,

Padmavathy²,

Saravanan³

et al. 2019

IJEAT

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A novel benzimidazole festooned pyrazolyl acrylonitrile 6 has been synthesized with a good yield via Knoevenagel condensation method and the structure has been elucidated based on analytical and spectroscopic methods. DFT-B3LYP calculation with 6-311 G(d,p) basis set has been performed for optimization of the structure and to determine their structural - energy parameters. The HOMO –LUMO analysis and polarizability cum hyper polarizability values ensure compound 6 is likely to be NLO material that could also find use in solar cells. Besides, the electronic properties and the structural cores imply that the molecule could also serve as bioagent.

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Novel aminopyrimidinyl benzimidazoles as potentially antimicrobial agents: Design, synthesis and biological evaluation

Cited by 119 publications

References 62 publications

A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis

A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis

A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis

Novel Benzimidazole Bejeweled Pyrazole: Synthesis, Characterization and Density Functional Theory Analysis

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