Cytostatic and Cytotoxic Activity of Synthetic Diterpene Derivatives Obtained from (-)-Kaur-9(11), 16-Dien-19-Oic Acid Against Human Cancer Cell Lines

Abstract

These diterpenes (1) and (2) were synthesized via epoxidation and rearrangements of (-)-Kaur-9(11), 16-dien-19-oate (7) isolated from Venezuelan species of espeletia (frailejón), and their antimicrobial and antitumoral activity were evaluated. Compound (1) showed GI 50 values of 51.6 nM against CNS SF-539, LC 50 = 100 µM, log 10 GI 50 = -7.29; compound (2) showed GI 50 at 4.17 µM against breast cancer T47D, LC 50 = 39 µM and Log 10 GI 50 = -5.38. Our results suggest that these compounds are highly cytotoxic and cytostatic against human cancer cell lines.

Cytotoxicity of synthetic derivatives against breast cancer and multi-drug resistant breast cancer cell lines: a literature-based perspective study

“…cell cycle Inhibited cancer cell proliferation results in cytostatic activity [73] Synthetic derivatives of novel N-substituted bis-benzimidazole, 9a, 9b, 9c, 9d, 9e, 9f, 9 g, 9 h, 9i 47D) where the derivatives participate in ROS and NO production through direct modification of proteins, lipids, and DNA that induces apoptosis in cancer cell lines. To that add this, synthetic oleanolic acid derivative HIMOXOL induced apoptotic pathway by activating caspase-8, caspase-3, and PARP-1 protein, elevating the ratio of Bax/ Bcl-2 protein level, triggering microtubule-associated protein LC3-II expression, and upregulating bectin 1 on MDA-MB-231 cell-line at IC 50 value 7.33 ± 0.79 μM [62].…”

Occurrence, Biological Activities and Synthesis of Kaurane Diterpenes and their Glycosides

“…Moreover, it was observed that only kaurenoic acid (1) and derivatives containing a free carboxyl group showed moderate antifungal activity against the dermatophytes assayed, suggesting that the presence of hydrophilic groups could be necessary for the observed antifungal activity. Alonso and collaborators [87] prepared diterpenes 50 and 51, among others, by an MCPBA epoxidation of grandiflorenic acid (9), isolated from species of the genus Espeletia (Asteraceae), followed by subsequent molecular rearrangement with borontrifluoride etherate or N-methyl-Nnitrosourea. Although these products had not presented, in general, any significant antimicrobial activity against Gram-positive or Gram-negative bacteria and yeasts (Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillus cereus, Candida tropicalis and Aspergillus niger), the rearranged diterpenes 50 and 51 revealed considerable cytotoxic activity against diverse neoplastic human cell lines such as colon, lung, leukemia, melanoma, ovary, kidney and prostate, with IG 50 values between 0.05 and 100 µM, indicating that these diterpenes (50 and 51) may be promising antitumoral substances.…”

Occurrence, Biological Activities and Synthesis of Kaurane Diterpenes and Their Glycosides

“…Alonso and collaborators [87] prepared diterpenes 50 and 51, among others, by an MCPBA epoxidation of grandiflorenic acid (9), isolated from species of the genus Espeletia (Asteraceae), followed by subsequent molecular rearrangement with borontrifluoride etherate or N-methyl-Nnitrosourea. Although these products had not presented, in general, any significant antimicrobial activity against Gram-positive or Gram-negative bacteria and yeasts (Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillus cereus, Candida tropicalis and Aspergillus niger), the rearranged diterpenes 50 and 51 revealed considerable cytotoxic activity against diverse neoplastic human cell lines such as colon, lung, leukemia, melanoma, ovary, kidney and prostate, with IG 50 values between 0.05 and 100 µM, indicating that these diterpenes (50 and 51) may be promising antitumoral substances.…”