Synthesis, Anticancer, and Antimicrobial Evaluation of Integerrimide‐A

Abstract

Integerrimide‐A (IG‐A) is a cyclic heptapeptide that was recently synthesized after being recovered from the latex of the Jatropha integerrima tree. This was achieved by first coupling a tetrapeptide unit (Boc‐Gly‐L‐Leu‐L‐Leu‐L‐Leu‐OMe) with a tripeptide unit (L‐Thr‐L‐Pro‐L‐Trp‐OMe). The characterization was done by using spectral techniques like FT‐IR, 1H‐NMR, mass spectrometry, and elemental analysis of the newly synthesized cyclic molecule. Antimicrobial and anticancer properties of IG‐A were tested using a biological screening. Gram +ve bacteria (B. subtilis and S. aureus) and Gram ‐ve bacteria (P. aeruginosa and E. coli) were used in the antibacterial testing. Fungal strains such as C. albicans, A. niger, T. mentagrophytes, and M. audouinii were used to test the antifungal activities. Antimicrobial activity analysis revealed that cyclic peptide—IG‐A (8)—has modest antibacterial activity and antifungal activities, when compared with the standard drugs ciprofloxacin and griseofulvin, respectively. Comparable MTT assays were performed on HCT116 (human colon carcinoma) and B16F10 (melanoma cells) cell lines with doxorubicin as the standard drug to determine the cytotoxic activity of the synthesized cyclic peptide. Inhibition of growth of HCT116 and B16F10 cell lines was used to calculate the cytotoxic effect. At a dosage of 120 μg/mL, the cyclopeptide IG‐A (8) inhibited cell proliferation by 87.5 and 72.5 percent, respectively. Cyclopeptide IG‐A had CTC50 values of 77.65 μM and 68.63 μM against HCT116 and B16F10, respectively. The % growth inhibitions at lesser levels are 72.5 and 50 at 60 μg/mL, respectively. The standard drug inhibited growth by 100 percent with CTC50 values of 48.63 μM and 43.25 μM against HCT116 and B16F10, respectively. From the results, it is concluded that IG‐A has considerable antimicrobial and cytotoxic effects. Internucleosomal DNA fragmentation may be the underlying mechanism in HCT116 cells, whereas the suppression of eumelanin synthesis in B16F10 cells is another possibility.