Novel Carboline Derivatives as Potent Antifungal Lead Compounds: Design, Synthesis, and Biological Evaluation

Wang, Shengzheng; Wang, Yan; Liu, Wei; Liu, Na; Zhang, Yongqiang; Dong, Guoqiang; Liu, Yang; Li, Zhengang; He, Xiaomeng; Miao, Zhenyuan; Yao, Jing; Li, Jian; Zhang, Wannian; Sheng, Chunquan

doi:10.1021/ml400492t

Cited by 50 publications

(53 citation statements)

References 35 publications

(55 reference statements)

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“…In particular, compounds 93 (A4) and 94 (A6) showed potent in vitro and in vivo anticryptococcal activity with good metabolic stability and BBB permeability. Moreover, the two compounds could significantly inhibit the melanin virulence factors at a concentration of 2.5 μM and might act by a new mode of action . The herbicide glyphosate ( 89 ) was identified to delay the melanization of C. neoformans in vivo and prolong mouse average lifetime, further suggesting that the in vivo inhibition of melanization might facilitate the control of C. neoformans infections …”

Section: Pigments Of Representative Colored Pathogens and Their Inhibmentioning

confidence: 99%

“…Moreover, the two compounds could significantly inhibit the melanin virulence factors at a concentration of 2.5 μM and might act by a new mode of action. 190,191 The herbicide glyphosate (89) was identified to delay the melanization of C. neoformans in vivo and prolong mouse average lifetime, further suggesting that the in vivo inhibition of melanization might facilitate the control of C. neoformans infections. 192 F I G U R E 2 1 A conceptualization of melanin organization and identified interactions with macromolecular structures in the cell wall of Cryptococcus neoformans.…”

Section: Melanin Inhibitors Against C Neoformans Infectionmentioning

confidence: 99%

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Targeting virulence factors as an antimicrobial approach: Pigment inhibitors

et al. 2019

Medicinal Research Reviews

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The fascinating and dangerous colored pathogens contain unique chemically pigmented molecules, which give varied and efficient assistance as virulence factors to the crucial reproduction and growth of microbes. Therefore, multiple novel strategies and inhibitors have been developed in recent years that target virulence factor pigments. However, despite the importance and significance of this topic, it has not yet been comprehensively reviewed. Moreover, research groups around the world have made successful progress against antibacterial infections by targeting pigment production, including our serial works on the discovery of CrtN inhibitors against staphyloxanthin production in Staphylococcus aureus. On the basis of the previous achievements and recent progress of our group in this field, this article will be the first comprehensive review of pigment inhibitors against colored pathogens, especially S. aureus infections, and this article includes design strategies, representative case studies, advantages, limitations, and perspectives to guide future research.

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Section: Pigments Of Representative Colored Pathogens and Their Inhibmentioning

confidence: 99%

Section: Melanin Inhibitors Against C Neoformans Infectionmentioning

confidence: 99%

Targeting virulence factors as an antimicrobial approach: Pigment inhibitors

et al. 2019

Medicinal Research Reviews

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“…Clinically, Aspergillus fumigatus (mortality rate: 50-90%), Cryptococcus neoformans (mortality rate: 20-70%), and Candida albicans (mortality rate: 20-40%) have been identied as the most common causes of fungal infections. [2][3][4] For the treatment of these infections, orally active polyenes (e.g., amphotericin B), 5) fluorinated pyrimidines (e.g., 5-fluorocytosine), azoles (e.g., fluconazole and voriconazole), 6) and echinocandins (e.g., caspofungin and micafungin), 7) have been widely used in clinic use 8) (Fig. 1).…”

Section: Synthesis Characterization and Antifungal Evaluation Of Novmentioning

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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“…3,4 Currently used antifungal drugs for the treatment of candidiasis include polyenes, azoles, echinocandins, allylamines, and ucytosine. 5 Among these, azole antifungals including uconazole, itraconazole, voriconazole, posaconazole, miconazole etc. are used in the treatment of both supercial and invasive fungal infections due to their broader antifungal spectrum and safety prole.…”

Section: Introductionmentioning

confidence: 99%