Total Synthesis of Clausenain, a Cyclic Octapeptide and its Analog for Anticancer Activity

Indian Journal of Pharmaceutical Education and Research

  • Nirmala Shinde1Department of Pharmaceutical Chemistry, S.M.B.T. College of Pharmacy, Nandi Hills, Dhamangaon. Igatpuri, Nashik, Maharashtra, INDIA.
  • Avinash Shridhar Dhake1Department of Pharmaceutical Chemistry, S.M.B.T. College of Pharmacy, Nandi Hills, Dhamangaon. Igatpuri, Nashik, Maharashtra, INDIA.
  • Kishan Prabhu Haval2Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, (Subcentre) Osmanabad, Maharashtra, INDIA.
  • Sachin Kawaduji Bhosale1Department of Pharmaceutical Chemistry, S.M.B.T. College of Pharmacy, Nandi Hills, Dhamangaon. Igatpuri, Nashik, Maharashtra, INDIA.

Volume 54 Issue 2s Pages s330-s336

DOI: 10.5530/ijper.54.2s.90

Abstract

Keeping in mind requisite of today’s era for development of new anticancer drugs, synthesis of a phenyl alanine rich cyclic octapeptide Clausenain and its analog by solution phase technique is described here. It was done through coupling a tetrapeptide BOC-Phe-Ser-Leu-Phe–OMe with another tetrapeptide BOC-Phe-Gly-Leu-Phe-OMe after proper deprotection towards carboxyl and amino terminals. The N-methyl analog of this octapeptide was prepared with N-methylated Glycine instead of Glycine as starting material. The linear peptides were then cyclized using suitable procedure. The establishment of structure for synthesized compounds was done by spectral and elemental analysis. Evaluation of synthesized compounds was done by brine shrimp lethality assay and further screening was done using a panel of 60 human tumor cell lines. The cyclic octapeptide and its analog showed good activity against cells lines of Leukemia, Non-small cell lung cancer, CNS cancer, breast cancer and renal cancer in comparison with vincristine as standard. The N-methylated analog was found to be more active than the cyclic peptide.

Keywords

  • Octapeptide
  • Solution phase technique
  • p-nitro phenyl ester method
  • Brine
  • shrimp
  • Anticancer
  • Tumor cell lines
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