title: Lysosome and HER3 (ErbB3) selective anticancer agent kahalalide F: semisynthetic modifications and antifungal lead-exploration studies.
abstract: Kahalalide F (1) shows remarkable antitumor activity against different carcinomas and has recently completed phase I clinical trials and is being evaluated in phase II clinical studies. The antifungal activity of this molecule has not been thoroughly investigated. In this report, we focused on acetylation and oxidation of the secondary alcohol of threonine, as well as reductive alkylation of the primary amine of ornithine, and each product was evaluated for improvements in antifungal activity. 1 and analogues do not exhibit antimalarial, antileishmania, or antibacterial activity; however, the antifungal activity against different strains of fungi was particularly significant. This series of compounds was highly active against Fusarium spp., which represents an opportunistic infection in humans and plants. The in vitro cytotoxicity for the new analogues of 1 was evaluated in the NCI 60 cell panel. Analogue 5 exhibited enhanced potency in several human cancer cell lines relative to 1.
authors: Department of Pharmacognosy, School of Pharmacy, The University of Mississippi, University, Mississippi 38677, USA.
authors: Abbas Gholipour
authors: AG
authors: Shilabin
authors: Noer
authors: N
authors: Kasanah
authors: David E
authors: DE
authors: Wedge
authors: Mark T
authors: MT
authors: Hamann
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000977:Antiparasitic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005670:Fusarium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000187:drug effects*; D008828:Microbiological Techniques; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009894:Opportunistic Infections / Q000382:microbiology; D021261:Parasitic Sensitivity Tests; D020893:Receptor, ErbB-3 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: C523905:4-fluorobenzylaminokahalalide F; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D000977:Antiparasitic Agents; D047630:Depsipeptides; C097897:kahalalide F; D020893:Receptor, ErbB-3
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