First report on the synthesis and structural studies of trans-Phakellistatin 18: a rotamer of marine natural product phakellistatin 18. Issue 9 (3rd May 2023)

• Record Type: Journal Article
• Authors: Kanwal, Iqra; Mushtaq, Farkhanda; Ali, Hunain; Tufail, Priya; Jahan, Humera; Shaheen, Farzana
• Is Part Of: Natural product research. Volume 37:Issue 9(2023)
• Page Start: 1470
• Page End: 1479
• Publication Date: 2023-05-03
• Subjects: Phakellistatin 18 -- Phakellia fusca; HepG2 cell line -- proline-rich cyclopeptide; Natural products -- Periodicals; Natural products -- Research -- Periodicals; Biological Factors -- Periodicals; Biological Products -- Periodicals; 547
• DOI: 10.1080/14786419.2021.2023141
• Languages: English
• ISSNs: 1478-6419

Abstract

Abstract: Phakellistatin peptides from marine organisms are the sources of proline-rich cyclic peptides with reported significant antitumor activities. Phakellistatin 18 (1 ), reported from marine sponge Phakellia fusca, contains three proline-peptide linkages in cis form. We attempted the total synthesis of natural product 1 through solution-phase macrocyclization approach, as a result, the synthetic cyclic peptide 2 was obtained as a rotamer of natural product having all three proline residues in trans -conformation. Here, we describe the synthesis, structural, and cytotoxicity studies of trans -Phakellistatin 18 (2 ), and its analog [Ala 1, 3, 6 ]-Phakellistatin 18 (3 ). Detailed NMR studies were carried out to characterize the synthesized peptides, and anti-cancer screening was performed by using MTT assay. The synthetic trans -Phakellistatin 18 (2 ) (IC50 =67.5 ± 2.938 µM) showed comparable cytotoxicity against HepG2 cancer cell line with standard drug doxorubicin (IC50 =63.88 ± 6.48 µM). Here, the first synthetic and structural studies on trans -Phakellistatin 18 (2 ), and its anticancer screening against HepG2 cell line was reported. Graphical Abstract: UF0001