Lanesoic Acid: A Cytotoxic Zwitterion from Theonella sp.

Abstract

Lanesoic acid (1) was isolated and characterized from Theonella sp. during PharmaMar's ongoing program to study cytotoxic substances from marine sources. Its planar structure, elucidated by spectral analysis (NMR, IR, UV, and MS), possesses an unusual skeleton containing a tetrahydropyrimidine cation that is stabilized as a zwitterion by an internal carboxylate counterion. The stereostructure of 1 was deduced from ROESY-NOESY, J-based configurational analysis (JBCA), and density functional theory (DFT) computational calculations fitted using the recently published DP4+ parameter. Compound 1 was moderately active and selective against pancreas PSN1 cells (IC = 8.9 μg/mL) and inactive against colon HT-29, breast MD-MB-23, and NSCLC lung tumor cells.

Marine natural products

“…Interestingly, 912 was moderately active against the pancreatic cancer PSN1 cell line (IC 50 ¼ 8.9 mg mL À1 ) but was inactive against colon, breast and lung tumour cells and hence shows cytotoxic specicity. 442 Jaspis splendens was the source of ve new alkaloids jaspterin 913, splendamide 914, jaspnin A 915, jaspamycin 916 and 6-bromo-1H-indole-3-carboximidamide 917, the latter two of which are known synthetically. 443 These compounds were discovered through the application of a novel, unbiased, phenotypic screen using a human olfactory neurosphere-derived cellular model of Parkinson's disease.…”

Cytotoxic Alkaloids Derived from Marine Sponges: A Comprehensive Review

“…133 displayed an unusual 1, 4, 5, 6-tetrahydropyrimidine cation rarely exhibits in natural sources. Compound 133 was evaluated for cytotoxicity against a panel of cell lines, such as PSN1, HT-29, breast MD-MB-231, and A549, that revealed selective cytotoxicity against PSN1cells with an IC50 value of 28.2 μM and was inactive against NSCLC lung tumor, MD-MB-23, and HT-29 cells [75]. The alkaloid variolin B (134), heterocyclic constitute from the Antractic sponge Kirkpatrickia variolosa had been evaluated for cytotoxicity against a wide range of cancer cell lines, where it showed potent activity against most of the tested cell lines with the activity against androgen-sensitive prostate adenocarcinoma cell line with GI50 0.05 μM [76].…”

Computational1H and13C NMR in structural and stereochemical studies

“…Advances of computational NMR in structural and stereochemical applications of 1 H and 13 C NMR chemical shifts and spin–spin coupling constants of natural products are very well documented in hundreds of original publications by a number of principal authors including (listed alphabetically) Alvarenga, [ 307,308 ] Bifulco, [ 309–313 ] Buevich, et al, [ 311,314–319 ] Cen‐Pacheko, [ 320–324 ] Kutateladze, [ 325–332 ] Saielli and Bagno, [ 333–340 ] Sarotti, [ 30,33,341,342 ] Tantillo (see comprehensive reviews by this author [ 343,344 ] and references given therein), Semenov and Krivdin, [ 345–349 ] and many others. [ 350–353 ]…”