Two new bromotyrosine derivatives, anomoian B (1) and aplyzanzine B (2), were isolated, respectively, from the organic extracts of a Verongida sponge belonging to the Hexadella genus and from a two-sponge association (Jaspis sp. and Bubaris sp.), both collected off the coast of Indonesia. The planar structure of 1 and 2 was determined by 1D and 2D NMR experiments and by high-resolution mass spectrometry, while their absolute stereochemistry was assigned by comparison with optical rotation values of known bromotyrosines and by chemical degradation. Both compounds showed moderate antiproliferative activity against a panel of different cancer cell lines. Their cytotoxic activity is facilitated through the induction of apoptosis, which is mediated neither by the generation of reactive oxygen species nor by the inhibition of histone deacetylases in these cell lines.

QM/NMR-DFT (quantum mechanics combined with nuclear magnetic resonance parameters calculated by density functional theory approximations) studies allowed us to link two stereoclusters separated by two methylene groups present in the new meroditerpenes halioxepine B (2) and halioxepine C (3) and the known halioxepine (1), isolated from two Indonesian sponges of the genus Haliclona (Reniera). DP4 and DP4+ probabilities were used to discriminate the two diastereotopic arrangements of the two stereoclusters, whose unconnected relative configurations were determined by ROESY and J-based configurational analysis. To confirm the DFT studies, the full relative configuration of 1 was deduced using a mixture of benzene-d and pyridine-d as the NMR solvent. ROESY measurements connected the two stereoclusters and demonstrated that DFT calculations accurately predict the configuration when two methylenes separate the two stereoclusters. The different arrangements of the distant stereoclusters C-1/C-2/C-7 and C-10/C-15 for compounds 2 and 3 were deduced by DFT calculations and explained the opposite optical rotations observed for the two compounds. Halioxepines B (2) and C (3) display moderate cytotoxicity against different human cancer cell lines.

A new macrolide, enigmazole C ( 1 ), and two additional analogues, enigmazoles E ( 2 ) and D ( 3 ), were obtained from a new species of the Homophymia genus as part of an ongoing discovery program at PharmaMar to study cytotoxic substances from marine sources. The structures were fully characterized by cumulative analyses of NMR, IR, and MS spectra, along with density functional theory computational calculations. All three of the new compounds feature an unusual 2,3-dihydro-4 H -pyran-4-one moiety, but only enigmazoles C ( 1 ) and D ( 3 ) showed cytotoxic activity in the micromolar range against A-549 (lung), HT-29 (colon), MDA-MB-231 (breast), and PSN-1 (pancreas) tumor cells.

JBCA and Marfey's allowed us to distinguish threonines diasteroisomers.

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.