Curcacycline A and B – new pharmacological insights to an old drug

Summary. Two cyclic peptides were isolated from the latex of Jatropha curcas L. (Figure1), namely curcacycline A and B. In the past both compounds have not been fully structure elucidated, today modern structure elucidation has been applied by more sophisticated bioanalytical techniques. Additionally, for the first time the structure was confirmed by a full synthetic approach and biological assays have been carried out to shed light on the pharmacological activity of both curcacyclines. Screening of antibiotic activity of curcacycline A was done against Bacillus subtilis ATCC 6633, Staphyloccus aureus ATCC 6538, Eschericia coli ATCC 8939, Pseudomonas aeruginosa ATCC 9027 and Candida albicans ATCC 10231 using paper disk diffussion method. Curcacycline A inhibited the growth of B. subtilis and P. aeruginosa with inhibition zone was ranged between 6.5 – 10.3 mm. Cytotoxic test show that it decreased the level of OVCAR 3 (ovarium cancer cell) at a concentration of 1 mg/mL, while no effect was found on Colo205 (human colon cancer cell). Curcacycline B did not have an effect on both cell lines. Brine shrimp cytotoxicity assay showed LD50 of curcacycline A and B at 49.85 μg/mL and 15.84 μg/mL, respectively. Both curcacyclines did not have a mutagenic effect on Salmonella typhimurium TA-98 and TA-mix (TA 7001, TA 7002, TA 7003, TA 7004, TA 7005, TA 7006). Industrial relevance. This study provides data on the safety as well the efficacy for curcacycline A and B. Curcacyline A possesses antimicrobial and cytotoxic activities. Based on AMES II assay, curcacycline A and B were proven not to be mutagenic. Both curcacyclines also can be synthesized in the lab. These data will be essential to develop curcacyclines as a new drug candidate for managing infectious and cancer diseases. Keywords. Curacycline; Jatropha curcas; cyclic peptides; brine shrimp assay; cytotxicity; MTS assay; AMES II test