Concise two-step chemical synthesis of molnupiravir.

A concise synthesis of molnupiravir in a one-pot two-step approach starting from uridine is described. Formally, herein, two sets of one-pot two-reaction steps introducing simplicity for purifications and using chemically available reagents are presented. In this context, molnupiravir was obtained in up to 68% overall yield and multigram-scale. In addition, HPLC analysis showed the molnupiravir purity above 99%.

Antischistosomal properties of aurone derivatives against juvenile and adult worms of Schistosoma mansoni.

Schistosomiasis is a neglected disease caused by helminth flatworms of the genus Schistosoma, affecting over 240 million people in more than 70 countries. The treatment relies on a single drug, praziquantel, making urgent the discovery of new compounds. Aurones are a natural type of flavonoids that display interesting pharmacological activities, particularly as chemotherapeutic agents against parasites. In pursuit of treatment alternatives, the present work conducted an in vitro and in vivo antischistosomal investigation with aurone derivatives against Schistosoma mansoni. After preparation of aurone derivatives and their in vitro evaluation on adult schistosomes, the three most active aurones were evaluated in cytotoxicity and haemolytic assays, as well as in confocal laser-scanning microscope studies, showing tegumental damage in parasites in a concentration-dependent manner with no haemolytic or cytotoxic potential toward mammalian cells. In a mouse model of schistosomiasis, at a single oral dose of 400 mg/kg, the selected aurones showed worm burden reductions of 35% to 65.0% and egg reductions of 25% to 70.0%. The most active thiophenyl aurone derivative 18, unlike PZQ, had efficacy in mice harboring juvenile S. mansoni, also showing significant inhibition of oviposition by parasites, giving support for the antiparasitic potential of aurones as lead compounds for novel antischistosomal drugs.

Screening of plant derived chalcones on the inhibition of potato apyrase: Potential protein biotechnological applications in health.

NTPDases (EC 3.6.1.5) are enzymes belonging to a protein family which have as a common feature the ability to hydrolyze di- and triphosphate nucleotides (ADP and ATP) to monophosphate nucleosides (AMP) in the presence of Ca+2 and Mg+. The potato apyrase has been the first protein of the NTPDase family to be purified. In mammals, these enzymes are involved in physiologic and sick processes as thromboregulation, inflammatory and immunologic responses. In this study, we investigated the in vitro potential of synthetic chalcones on the inhibition of potato apyrase purified from Solanum tuberosum. The protein was purified with high grade purity and its identity was confirmed by electrophoresis, western blot, and LC-MS/MS. Five out of the eight chemically synthetized chalcones analyzed in this study showed significant inhibition of the apyrase activity. The compound with the best rate of inhibition of ATP hydrolytic activity was able to promote 54% inhibition with a concentration of 3.125 µM. Ticlopidine, used as an inhibition drug control, was able to promote inhibitions around 50% of the activity (IC50 = 2.167 µM). Our results with the potato apyrase inhibition with the synthetic chalcones suggest that these compounds may use as potential lead candidates for the treatment of some diseases associated with nucleotides.

In Vitro and in Vivo Antischistosomal Activities of Chalcones.

In this study, we evaluated the in vitro and in vivo schistosomicidal activities of chalcones against Schistosoma mansoni worms. In vitro assays revealed that chalcones 1 and 3 were the most active compounds, without affecting significantly mammalian cells. Confocal laser scanning microscopy and scanning electron microscopy studies revealed reduction on the numbers of tubercles and morphological alterations in the tegument of S. mansoni worms after in vitro incubation with chalcones 1 and 3. In a mouse model of schistosomiasis, the oral treatment (400 mg/kg) with chalcone 1 or 3 significantly caused a total worm burden reduction in mice. Chalcone 1 showed significant inhibition of the S. mansoni ATP diphosphohydrolase activity, which was corroborated by molecular docking studies. The results suggested that chalcones could be explored as lead compounds with antischistosomal properties.