Peptide‐Heterocycle Conjugates as Antifungals Against Cryptococcosis. Issue 7 (24th June 2022)

• Record Type: Journal Article
• Authors: Sharma, Krishna K.; Sharma, Komal; Kudwal, Anurag; Khan, Shabana I.; Jain, Rahul
• Is Part Of: Asian journal of organic chemistry. Volume 11:Issue 7(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-24
• Subjects: Antifungal -- Cryptococcosis -- Cytotoxicity -- Heterocycle-peptide conjugates -- Peptidomimetics; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; 547.005
• DOI: 10.1002/ajoc.202200196
• Languages: English
• ISSNs: 2193-5807

Abstract

Abstract: In last three decades, only one new USFDA approved antifungal drug (echinocandin) was introduced into the clinics. The identification of new scaffolds with novel mechanisms of action is an important goal of current antifungal research. Herein, we describe the design, synthesis and in vitro antimicrobial activities of heterocycle‐His(2‐aryl)‐Arg‐NHBzl conjugates as a new structural class of peptidomimetics with promising antifungal activity against Cryptococcus neoformans (IC50 values ranging between 2.13–14.57 μg mL −1 ). The most potent analog, quinolinyl‐His(2‐ tert ‐butylphenyl)‐Arg‐NHBzl (17 f ) exhibited IC50 and MIC values of 2.13 and 2.50 μg mL −1, respectively against C. neoformans . Abstract : This work describes the synthesis and biological activity of peptide‐heterocycle conjugates [heterocycle‐His(2‐aryl)‐Arg‐NHBzl] as a new structural class of antifungals displaying promising activity against Cryptococcus neoformans . The designed analogs were synthesized applying a rapid microwave‐assisted solution phase peptide synthesis protocol. The lead compound, quinolinyl‐His(2‐ tert ‐butylphenyl)‐Arg‐NHBzl (17 f ) exhibited IC50 and MIC values of 2.13 and 2.50 μg mL −1, respectively. The conjugate was non‐cytotoxic confirming its potential as new identified lead.