Marine organisms represent almost half of total biodiversity and are a very important source of new bioactive substances. Within the varied biological activities found in marine products, their antimicrobial activity is one of the most relevant. Infectious diseases are responsible for high levels of morbidity and mortality and many antimicrobials lose their effectiveness with time due to the development of resistance. These facts justify the high importance of finding new, effective and safe anti-infective agents. Among the variety of biological activities of marine xanthone derivatives, one that must be highlighted is their anti-infective properties. In this work, a literature review of marine xanthones with anti-infective activity, namely antibacterial, antifungal, antiparasitic and antiviral, is presented. Their structures, biological activity, sources and the methods used for bioactivity evaluation are described. The xanthone derivatives are grouped in three sets: xanthones, hydroxanthones and glycosylated derivatives. Moreover, molecular descriptors, biophysico-chemical properties, and pharmacokinetic parameters were calculated, and the chemical space occupied by marine xanthone derivatives is recognized. The chemical space was compared with marketed drugs and framed accordingly to the drug-likeness concept in order to profile the pharmacokinetic of anti-infective marine xanthone derivatives.

Squaraine dyes have recently attracted interest as potential second generation photosensitizers for photodynamic therapy. Several cationic aminosquaraine dyes bearing benzoselenazole terminal nuclei were synthezised and their cytotoxic activity was tested against four different human tumor cell lines – breast (MCF-7), non-small cell lung (NCI-H460), cervical (HeLa) and hepatocellular (HepG2) carcinomas – and against a non-tumor porcine liver primary cell line (PLP2), both in the absence of light and under irradiation. All dyes, which displayed strong absorption within the phototherapeutic window, were found to exhibit photodynamic activity and were shown to be, in most cases, more cytotoxic, both in the dark and upon irradiation, than their benzothiazole analogues.

Optimized syntheses of (E)-5-(2-ethoxyphenyl)-N-(3-(methylsulfonyl)allyl)-1H-pyrazole-3-carboxamide (RA-0002034, 1), a promising antiviral covalent cysteine protease inhibitor lead, were developed. The syntheses avoid the contamination of 1 with the inactive cyclic dihydropyrazolo[1,5-a]pyrazin-4(5H)-one 2, which is formed by the intramolecular aza-Michael reaction of the vinyl sulfone warhead under basic conditions and slowly at pH 7.4 in phosphate buffer. The pure cysteine protease inhibitor 1 could be synthesized using either modified amide coupling conditions or through the introduction of a MOM-protecting group and was stable as a TFA or HCl salt. Although acyclic 1 demonstrated poor pharmacokinetics with high in vivo clearance in mice, inactive cyclic 2 showed improved plasma exposure. The potential use of cyclic dihydropyrazolo[1,5-a]pyrazin-4(5H)-ones as prodrugs for the acyclic β-amidomethyl vinyl sulfone warhead was demonstrated by GSH capture experiments with an analog of 2.

Co-catalytic proline and phosphate accelerate prebiotic aldol chemistry, setting the stage for a transition to enzymatic metabolism and highlighting the importance of general acid-based catalysis.

Optimized syntheses of (E)-5-(2-ethoxyphenyl)-N-(3-(methylsulfonyl)allyl)-1H-pyrazole-3-carboxamide (RA-0002034, 1), a promising antiviral covalent cysteine protease inhibitor lead, were developed. The syntheses avoid the contamination of 1 with the cyclic dihydropyrazolo[1,5-a]pyrazin-4(5H)-one 2, which formed by intramolecular aza-Michael reaction of the vinyl sulfone warhead under basic conditions and at pH 7.4 in phosphate buffer. 1 could be synthesized using either modified amide coupling conditions or through introduction of a MOM-protecting group and was stable as a TFA or HCl salt. Although acyclic 1 demonstrated poor pharmacokinetics with high in vivo clearance in mice, the cyclic 2 showed improved plasma exposure. The potential use of dihydropyrazolo[1,5-a]pyrazin-4(5H)-ones as prodrugs for the acyclic beta-amidomethyl-vinyl sulfone warhead was demonstrated by GSH capture experiments.