Structure-activity relationship studies of ultra-short peptides with potent activities against fluconazole-resistant Candida albicans
| Autor: | Kiat Whye Kong, Qiu Ying Lau, Mohammad Alfatah, Shawn Hoon, Prakash Arumugam, Fui Mee Ng, Timothy Barkham, Siew Mei Samantha Ng, Jeffrey Hill, Jeanette W. P. Teo, Cheng San Brian Chia, Esther H. Q. Ong, Jia Mao Yap |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Drug Antifungal Agents Cell Survival media_common.quotation_subject 030106 microbiology Antimicrobial peptides Antifungal drug Microbial Sensitivity Tests Microbiology 03 medical and health sciences Structure-Activity Relationship Drug Resistance Fungal Drug Discovery Candida albicans medicine Humans Peptide library Fluconazole media_common Pharmacology biology Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry General Medicine Fibroblasts Antimicrobial biology.organism_classification Corpus albicans 030104 developmental biology Peptides medicine.drug |
| Zdroj: | European journal of medicinal chemistry. 150 |
| ISSN: | 1768-3254 |
| Popis: | Vulvovaginal candidiasis (VVC) is a genital fungal infection afflicting approximately 75% of women globally and is primarily caused by the yeast Candida albicans. The extensive use of fluconazole, the first-line antifungal drug of choice, has led to the emergence of fluconazole-resistant C. albicans, creating a global clinical concern. This, coupled to the lack of new antifungal drugs entering the market over the past decade, has made it imperative for the introduction of new antifungal drug classes. Peptides with antifungal properties are deemed potential drug candidates due to their rapid membrane-disrupting mechanism of action. By specifically targeting and rapidly disrupting fungal membranes, they reduce the chances of resistance development and treatment duration. In a previous screening campaign involving an antimicrobial peptide library, we identified an octapeptide (IKIKIKIK-NH2) with potent activity against C. albicans. Herein, we report a structure-activity relationship study on this peptide with the aim of designing a more potent peptide for further development. The lead peptide was then tested against a panel of fluconazole-resistant C. albicans, subjected to a fungicidal/static determination assay, a human dermal fibroblast viability assay and a homozygous profiling assay to gain insights into its mechanism of action and potential for further development as a topical antifungal agent. |
| Databáze: | OpenAIRE |
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