Marine-Derived Macrocyclic Alkaloids (MDMAs): Chemical and Biological Diversity

The curiosity and attention that researchers have devoted to alkaloids are due to their bioactivities, structural diversity, and intriguing chemistry. Marine-derived macrocyclic alkaloids (MDMAs) are considered to be a potential source of drugs. Trabectedin, a tetrahydroisoquinoline derivative, has been approved for the treatment of metastatic soft tissue sarcoma and ovarian cancers. MDMAs displayed potent activities that enabled them to be used as anticancer, anti-invasion, antimalarial, antiplasmodial, and antimicrobial. This review presents the reported chemical structures, biological activities, and structure–activity relationships of macrocyclic alkaloids from marine organisms that have been published since their discovery until May 2020. This includes 204 compounds that are categorized under eight subclasses: pyrroles, quinolines, bis-quinolizidines, bis-1-oxaquinolizidines, 3-alkylpiperidines, manzamines, 3-alkyl pyridinium salts, and motuporamines

Bioactivity and molecular docking of lactones isolated from Centaurea pseudosinaica Czerep

Two cytotoxic sesquiterpene lactones, 17-epichlorohyssopifolin A (1) and chlorjanerin (2), and a monoterpene lactone, loliolide (3) were isolated from Centaurea pseudosinaica. The cytotoxicity of the total extract and terpenoids 1–3 were evaluated against three human cancer cells (HepG2, PC-3, and HT-29), along with the human normal primary epidermal keratinocytes (HEKa) cells. With IC50 values ranging between 0.6 ± 0.04 and 5.0 ± 0.61 μg/mL against HepG2; 0.2 ± 0.01 and 11.9 ± 1.31 μg/mL against PC-3, and 0.04 ± 0.013 and 8.9 ± 0.97 μg/mL against HT-29, the total extract, and lactones 1–3 demonstrated cytotoxic effects. Compound 1 displayed the strongest impact on all cancer cells and a slightly safe effect on the normal cells HEKa. Compound 1 caused accumulation of HepG2 and HT-29 cells in G1 phase as displayed cell cycle analysis. On the other hand, the cell distributions were increased in the S phase in PC-3 cells. Furthermore, 1 caused apoptosis in PC-3 and HePG2 cells with 91.50%, and 79.72 %, respectively. A higher fraction of necrotic cells was observed in HT-29 cells amounting to 23.60%. These results suggested that the promising cytotoxicity exhibited by 1 is brought by the apoptosis induction in the cancer cells, which were evaluated. As the compounds showed antiproliferative effect against the HT-29 cells, the docking simulation was performed aiming at determining how they would interact with the EGFR enzyme, whose PDB: 4I23 is considered one of the two distinct wild types of EGFR enzymes. The antibacterial activity results revealed that 3 showed the most remarkable antibacterial effects, especially against the examined Gram-positive bacteria. The total extract exhibited potent activity against all examined bacteria. The total extract showed a potent antifungal effect against two Candida and two Aspergillus pathogens. The antioxidant activity revealed the potency of the total extract and 3 as antioxidant candidates. The obtained results refer to the importance of Centaurea pseudosinaica as a source of potent antiproliferative agents and the whole plant as an antipathogenic and antioxidant agent

Arene-Perfluoroarene-Anion Stacking and Hydrogen Bonding Interactions in Imidazolium Salts for the Crystal Engineering of Polarity

The crystal structure of 1-(2,3,5,6-tetrafluoropyridyl)-3-benzylimidazolium bromide possesses C₆H₅···C₅F₄N···Br^– interactions that link the cations into chains, N­(C)­C–H···Br^– interactions that link the chains into sheets, and N₂C–H···Br^– interactions that link the sheets to one another. As a consequence of these, it is polar (<i>Pna</i>2₁). Density functional theory calculations indicate that the strength of the interaction between a cation and a bromide anion lies in the order N₂C–H···Br^– > N­(C)­C–H···Br^– > C₆H₅···C₅F₄N···Br^–. Prevention of the N₂C–H···Br^– interaction by substitution of the hydrogen atom with a methyl group leads to dimers linked by two C₆H₅···C₅F₄N···Br^– interactions. Prevention of the N­(C)­C–H···Br^– interaction by substitution of the hydrogen with a methyl group permits chains of cations, but because the N₂C–H···Br^– interactions link the chains there are no strong interactions between the sheets. Chains of cations linked by Ar···C₅F₄N···Br^– interactions also arise when the benzyl group is replaced by 3-phenylbenzyl and 2-naphthylmethyl groups. The former also contains N₂C–H···Br^– and N­(C)­C–H···Br^– interactions and is centrosymmetric. The latter does not contain N­(C)­C–H···Br^– interactions and is chiral and polar (<i>P</i>2₁). Exchanging the positions of the aryl and polyfluoroaryl groups results in a crystal structure with no π–π stacking between the aryl and polyfluoroaryl groups although N₂C–H···Br^– and N­(C)­C–H···Br^– interactions persist