Abstract
A solution phase method was adopted for the synthesis of proline-containing cyclic pentapeptide 2 and total synthesis of naturally occurring cyclic heptapeptide Reniochalistatin B 3. For the synthesis of 3, both divergent and convergent strategies were used to improve the overall yield from 12 to 25%. Different N and C terminal modified linear analogs and congeners of 2 and 3 were synthesized. Both cyclic peptides 2 and 3 and their linear analogs/congeners were evaluated for anti-cancer activity against HeLa cell line, among which pentapeptide 2 h and hexapeptide 3n with N-terminal protected hexafluoroisopropyl carbamates (HFIPC) interestingly showed higher cytotoxicity with an IC50 of 2.73 and 4.3 µM, respectively compared to their Boc-protected analogs 2a (IC50 20 µM) and 3c (IC50 38.51 µM) and cyclic peptides 2 (>100 µM) and 3 (47 µM). These results were further validated by biological experiments such as colony formation and wound healing assays.
Graphical Abstract
![](/cms/asset/993af30e-1979-4795-aff2-353216536531/lsyc_a_1550201_uf0001_c.jpg)
Acknowledgment
K.C.G. is thankful to CSIR, New Delhi for his fellowship. C.B. is grateful to DST-WOS A for her fellowship. P.B. thanks DBT-RA for financial support.