Divergent Approach for the Synthesis of Gombamide A and Derivatives.
A synthesis of gombamide A (1) using N-terminal peptide extension, oxidative disulfide bond formation, and late-stage 4-hydroxystyrylamide installation has been achieved. This divergent method was also utilized to synthesize several gombamide A derivatives with modification to the 4-hydroxystyrylamide via cyclic peptide 2. The natural product and four derivatives were found to be devoid of Na(+)/K(+)-ATPase activity at 10 μM. In addition, the compounds were not cytotoxic at 10 μM against a panel of cancer cells.
Department of Pharmacological and Pharmaceutical Sciences, University of Houston , Science and Research Building 2, Room 549A, Houston, Texas 77204, United States.
Mohana Rao
MR
Vippila
Department of Pharmacological and Pharmaceutical Sciences, University of Houston , Science and Research Building 2, Room 549A, Houston, Texas 77204, United States.
Sameer
S
Nikhar
Department of Pharmacological and Pharmaceutical Sciences, University of Houston , Science and Research Building 2, Room 549A, Houston, Texas 77204, United States.
Alan P
AP
Gracia
Department of Pharmacological and Pharmaceutical Sciences, University of Houston , Science and Research Building 2, Room 549A, Houston, Texas 77204, United States.
Gregory D
GD
Cuny
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D010456:Peptides, Cyclic; C584229:gombamide A; D000254:Sodium-Potassium-Exchanging ATPase