Cytotoxicity of synthetic racemic ptilocaulin: A novel cyclic guanidine

Abstract

(+)-Ptilocaulin, a novel cyclic guanidine extracted from the Caribbean sponge Ptilocaulis aff. P. Spiculifer, is reported to have broad spectrum antimicrobial activity in vitro as well as in vitro activity against L1210 murine leukemia. To more fully evaluate this compound as an anticancer agent, the in vitro cell growth inhibitory potencies of synthetic racemic ptilocaulin and ten clinical anticancer drugs were determined and compared in 16 different normal and transformed human and murine cell populations. Potency, expressed as the 50% inhibitory concentration (IC50), was determined by a tetrazolium reduction (MTT) assay. Ptilocaulin showed a fairly broad spectrum of in vitro activity against colon and mammary adenocarcinomas, melanomas, leukemias, transformed fibroblasts and normal lymphoid cells (IC50s 0.05- greater than 10 micrograms/ml). This activity was comparable to that of many of the clinical drugs, including vinca alkyloids, antibiotics, alkylators and antimetabolites. Cell viability was affected only after a 72 hr exposure to the compound. In a clonogenic assay, cytocidal effects were observed after 24-72 hr exposures to 10 x IC50 concentrations of ptilocaulin, as evidenced by failure of cells to resume growth after removal of the compound. Cytostatic effects were observed at less than or equal to IC50 concentrations, as evidenced by resumption of growth to near-control levels after removal of the compound. Ptilocaulin was toxic at 50 and 25 mg/kg in an in vivo L1210 tumor model and was ineffective at lower concentrations (T/Cs 100-112%). In vivo studies in a more sensitive tumor system are recommended but are limited by the lack of availability of sufficient quantities of the compound.

Guanidine Alkaloids from Monanchora arbuscula: Chemistry and Antitumor Potential

“…For this same line, Ruben et al [22] obtained the average IC 50 value of 0.13 mg/ ml with a synthetic racemic ptilocaulin. The values determined in the present study, however, present a tenfold higher IC 50 array (on HL-60, IC 50 ¼ 5.77 mm corresponds to Hemolysis: ca.…”

Synthesis of Condensed Heterocycles, Containing Partially Saturated Pyrimidine Nuclei, from Aromatic Pyrimidine Derivatives

“…Ptilomycalin A displays significant activity against a series of cancer cell lines and DNA polymerase activity of the reverse transcriptase of human immunedeficiency virus type 1 . The tricyclic guanidine ptilocaulin and crambescin A is reported to have a broad spectrum antimicrobial activity in vitro as well as in vivo activity against L1210 murine leukemia.…”

Netamines O–S, Five New Tricyclic Guanidine Alkaloids from the Madagascar Sponge Biemna laboutei, and Their Antimalarial Activities

“…Introduction. -T ricyclic guanidinec ompounds,b earingatricyclic 2-amino-1,3diazaoctahydroacenaphtylene skeleton, like ptilocaulins,mirabilins, and netamines,are restricted to marine sponges of the order Poecilosclerida [1 -11] and can be grouped on the basis of their degree of oxidation and C¼Cb ond position with pyrimidine, D 7, 8 -, D 8,8a -, D 8a,8b -unsaturated, or saturated heterocycles.M any of these alkaloids were reported to possess noteworthy biological activities, i.e.,c ytotoxic [1] [4] [8] [9] [12], antibacterial [1] [7], antifungal [3], antimalarial [3] [11],a nd antiprotozoal activities [3].…”

“…No correlation was observed between these three Hatoms and HÀC 8 . Thec ytotoxic activity of a synthetic racemic ptilocaulin was studied by Rubent et al [12]inorder to evaluate its in vitro activitiesa gainstv arious cell lines.M oreover, the authors have shown that ptilocaulin was toxic at 50 and 25 mg kg À 1 in an in vivo L1210 tumor model and was ineffective at lower concentrations (T/C 100 -112%).…”