含硼之胜肽衍生物合成與其生物活性之評估(I);含硼之異腈衍生物之合成(II)

Abstract

Synthesis and Biological Evaluation of Boron-Containing Peptide-Based Analogues(I) In this research, we have designed and synthesized two series of boron-containing analogues. These compounds could be easily synthesized and purified via simple synthetic operations. In addition, MTT assay was applied to evaluate their biological potencies against HepG2 (liver cancer), and MDA-MB231 (drug resistant breast cancer). Compounds A-07, A-08, A-09, A-11 and A-12 potent against HepG2(liver cancer) cell line. B-38, B-41, B-42 are active against MDA-MB231(drug resistant breast cancer) cell line and B-41, B-42 are potent against HepG2 cancer cell line. The structure-activity relationship (SAR)indicated that compounds possess lager side chain were generally more potent against either HepG2 or MDA-MB231 cell lines. In addition, inclusion of a potassium trifluoroborate was essential to the compound’s biological activity. In summery, inclusion of a phenylalanine at position 2, a benzyl-protected serine at position 3 and a potassium trifluoroborate generated the most potent compound (B41) against HepG2 and MDA-MB231 cell lines. Synthesis of Boron-Containing Isocyanide Analogues(II) In the second project, we have designed and synthesized boron-containing isocyanide. The overall yield was 58% over 9 steps synthetic operations. More boron-containing isocyanide derivatives were being synthesized and their biological evaluation will be reported in due course.