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
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.