Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 3

Kawasaki, Ken-íchi; Masubuchi, Miyako; Morikami, Kenji; Sogabe, Satoshi; Aoyama, Tsunehisa; Ebiike, Hirosato; Niizuma, Satoshi; Hayase, Michiko; Fujii, Toshihiko; Sakata, Kiyoaki; Shindoh, Hidetoshi; Shiratori, Yasuhiko; Aoki, Yuko; Ohtsuka, Tatsuo; Shimma, Nobuo

doi:10.1016/s0960-894x(02)00844-2

Cited by 98 publications

(57 citation statements)

References 15 publications

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“…Molecular Docking In an attempt to correlate the SARs with the binding mode of the synthesized compounds, the benzofuran inhibitor 1 which was reported as NMT inhibitor by Ohtsuka and colleagues 23) and 4o were docked into the crystal structure of NMT from C. alb. (CaNMT).…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Characterization and Antifungal Evaluation of Novel Thiochromanone Derivatives Containing Indole Skeleton

Han

Zhong

et al. 2016

Chem. Pharm. Bull.

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Invasive fungal disease constitutes a growing health problem and development of novel antifungal drugs with high potency and selectivity against new fungal molecular targets are urgently needed. In order to develop potent antifungal agents, a novel series of 6-alkyl-indolo[3,2-c]-2H-thiochroman derivatives were synthesized. Microdilution broth method was used to investigate antifungal activity of these compounds. Most of them showed good antifungal activity in vitro. Compound 4o showed the best antifungal activity, which (inhibition of Candida albicans and Cryptococcus neoformans) can be achieved at the concentration of 4 µg/mL. Compounds 4b (inhibition of Cryptococcus neoformans), 4j (inhibition of Cryptococcus neoformans), 4d (inhibition of Candida albicans) and 4h (inhibition of Candida albicans) also showed the best antifungal activity at the concentrations of 4 µg/mL. The molecular interactions between 4o and the N-myristoyltransferase of Candida albicans (PDB ID: 1IYL) were finally investigated through molecular docking. The results indicated that these thiochromanone derivatives containing indole skeleton could serve as promising leads for further optimization as novel antifungal agents.

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Section: Resultsmentioning

confidence: 99%

Synthesis, Characterization and Antifungal Evaluation of Novel Thiochromanone Derivatives Containing Indole Skeleton

Han

Zhong

et al. 2016

Chem. Pharm. Bull.

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“…Up to now, various types of NMT inhibitors such as peptidomimetic [10][11][12], myristic acid analogues [13] and different kinds of heterocycles [14][15][16] have been reported. Among them, benzofuran inhibitors showed high selectivity and powerful antifungal activity [16][17][18][19] (Figure 1). Furthermore, the benzofuran core itself possessed a definite antifungal activity and numbers of benzofuran derivatives were reported without indicating the targets [20][21][22][23] In recent years, the 1,2,3-triazole scaffold became a highlight fragment with the emergence of click chemistry and the 1,2,3-triazole-containing compounds were reported to possess a variety of biological activities [24][25][26][27][28], especially as antifungal agents [29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Antifungal Activity of Novel Benzofuran-Triazole Hybrids

Liang

Tian

et al. 2016

Molecules

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Abstract:A series of novel benzofuran-triazole hybrids was designed and synthesized by click chemistry, and their structures were characterized by HRMS, FTIR and NMR. The in vitro antifungal activity of target compounds was evaluated using the microdilution broth method against five strains of pathogenic fungi. The result indicated that the target compounds exhibited moderate to satisfactory activity. Furthermore, molecular docking was performed to investigate the binding affinities and interaction modes between the target compound and N-myristoyltransferase. Based on the results, preliminary structure activity relationships (SARs) were summarized to serve as a foundation for further investigation.

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“…Invasive fungal infections have increased dramatically in recent years to become important causes of morbidity and mortality in hospitalized patients [1][2][3]. N-myristoyltransferase (NMT) has been a promising new target for the design of novel antifungal agents with new mode of action.…”

Section: Introductionmentioning

confidence: 99%

“…Imidazoles are important class of compounds that have shown multiple therapeutic actions and have been widely used including as antifungals [7,8]. There is a report that compounds containing furan nucleus exhibited inhibitory effect on NMT of C. albicans [9,10] and antimicrobial [11,12] activities. In view of the potential pharmacophoric nature of imidazole and furan nucleus and affinity of furan nucleus with NMT [13], compounds containing both imidazole and furan nucleus were designed rationally with the aim to have synergistic effect on target, synthesized and evaluated for their antifungal activity.…”

Section: Introductionmentioning

confidence: 99%

Search of New Scaffolds against N-myristoyltransferase for Antifungal Activity

Vengurlekar¹,

Gupta²

2016

MOCR

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Abstract. N -myristoyltransferase (NMT) has been an emerging target for the design of novel antifungal agents with new mode of action. A series of furan and imidazole containing heterocyclic derivatives have been designed using rational drug designing approach as NMT inhibitors. Newly Designed compounds were synthesized, characterized and evaluated for their antifungal activity against NMT. Synthesized compounds were characterized by IR, NMR and Mass. In vitro antifungal assay indicated that these derivatives have shown moderate to good antifungal activity against five fungal strains. A possible antifungal target was identified (NMT) and furan derivatives showed more favorable affinity than the imidazole ligands.

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Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 3

Cited by 98 publications

References 15 publications

Synthesis, Characterization and Antifungal Evaluation of Novel Thiochromanone Derivatives Containing Indole Skeleton

Synthesis, Characterization and Antifungal Evaluation of Novel Thiochromanone Derivatives Containing Indole Skeleton

Design, Synthesis and Antifungal Activity of Novel Benzofuran-Triazole Hybrids

Search of New Scaffolds against N-myristoyltransferase for Antifungal Activity

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