title: Synthesis of Natural Acylphloroglucinol-Based Antifungal Compounds against Cryptococcus Species.
abstract: Thirty-three natural-product-based acylphloroglucinol derivatives were synthesized to identify antifungal compounds against Cryptococcus spp. that cause the life-threatening disseminated cryptococcosis. In vitro antifungal testing showed that 17 compounds were active against C. neoformans ATCC 90113, C. neoformans H99, and C. gattii ATCC 32609, with minimum inhibitory concentrations (MICs) in the range 1.0-16.7 μg/mL. Analysis of the structure and antifungal activity of these compounds indicated that the 2,4-diacyl- and 2-acyl-4-alkylphloroglucinols were more active than O-alkyl-acylphloroglucinols. The most promising compound found was 2-methyl-1-(2,4,6-trihydroxy-3-(4-isopropylbenzyl)phenyl)propan-1-one (11j), which exhibited potent antifungal activity (MICs, 1.5-2.1 μg/mL) and low cytotoxicity against the mammalian Vero and LLC-PK1 cell lines (IC50 values >50 μg/mL). This compound may serve as a template for further synthesis of new analogues with improved antifungal activity. The findings of the present work may contribute to future antifungal discovery toward pharmaceutical development of new treatments for cryptococcosis.
authors: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University , Nanjing, 211198, People's Republic of China.
authors: Qian
authors: Q
authors: Yu
authors: Ranga Rao
authors: RR
authors: Ravu
authors: Melissa R
authors: MR
authors: Jacob
authors: Shabana I
authors: SI
authors: Khan
authors: Ameeta K
authors: AK
authors: Agarwal
authors: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University , Nanjing, 211198, People's Republic of China.
authors: Bo-Yang
authors: BY
authors: Yu
authors: Xing-Cong
authors: XC
authors: Li
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D056285:Cryptococcus gattii / Q000187:drug effects; D003455:Cryptococcus neoformans / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010696:Phloroglucinol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D010696:Phloroglucinol