Identification of Dihydropyrazolo[1,5-]pyrazin-4(5)-ones as Cyclic Products of β-Amidomethyl Vinyl Sulfone Alphavirus Cysteine Protease Inhibitors.

Optimized syntheses of ()-5-(2-ethoxyphenyl)--(3-(methylsulfonyl)allyl)-1-pyrazole-3-carboxamide (RA-0002034, ), a promising antiviral covalent cysteine protease inhibitor lead, were developed. The syntheses avoid the contamination of with the inactive cyclic dihydropyrazolo[1,5-]pyrazin-4(5)-one , 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.

Prebiotic triose glycolysis promoted by co-catalytic proline and phosphate in neutral water.

Proline and phosphate promote a near-quantitative aldol reaction between glycolaldehyde phosphate and formaldehyde at neutral pH in water. Our results demonstrate the important role of general acid-base catalysis in water and underscore the essential role that amino acid catalysis may have played in early evolution of life's core metabolic pathways.

Yicathins B and C and Analogues: Total Synthesis, Lipophilicity and Biological Activities.

Natural products have always been an important source of new hits and leads in drug discovery, with the marine environment being regarded as a significant source of novel and exquisite bioactive compounds. Yicathins B and C are two marine-derived xanthones that have shown antibacterial and antifungal activity. Herein, the total synthesis of these yicathins and six novel analogues is reported for the first time.

Structures, Activities and Drug-Likeness of Anti-Infective Xanthone Derivatives Isolated from the Marine Environment: A Review.

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.

Synthesis, photochemical and in vitro cytotoxic evaluation of benzoselenazole-based aminosquaraines.

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.

Aminosquaraines as potential photodynamic agents: Synthesis and evaluation of in vitro cytotoxicity.

The synthesis of several aminosquaraine cationic dyes displaying strong absorption within the so-called phototherapeutic window (650-850nm) is described. Their cytotoxicity, under dark and illuminated conditions, was tested against several human tumor cell lines (breast, lung, cervical and hepatocellular carcinomas) and non-tumor porcine liver primary cells. All compounds showed to inhibit the growth of the tumor cells upon irradiation more than in the absence of light, in more or less extension, clearly exhibiting photodynamic activity.