Abstract The genus Clusia L. is highly diverse in Central and South America, comprising about 300 species, including trees and shrubs, hemiepiphytes, epiphytes, and lianas. This genus deserves attention due to its wide range of biological activities. Clusia belongs to the Clusiaceae family, chemically characterized by the presence of xanthones, benzophenones, flavonoids, coumarins, terpenoids, and other substances with bioactive activity already described. This review aims to highlight the biological activity associated to extracts and isolated substances from species of the Clusia genus, including anti-HIV, antimicrobial, antioxidant, antinociceptive, antitumor, leishmanicidal, modulator of inflammatory processes, neutralization of toxic effects caused by snake bites, and others. This review gathered information on biological activities associated with different types of extracts and isolated substances of the genus Clusia, traditional use, chemical profile, and biological properties of plants of the genus, published in the last 23 years (1998 to 2021) and that can provide support for future research. The paper aims to provide an overview of existing knowledge about the biological properties of the genus Clusia plant species. L America 30 shrubs hemiepiphytes epiphytes lianas family xanthones benzophenones flavonoids coumarins terpenoids described antiHIV, antiHIV anti HIV, HIV anti-HIV antimicrobial antioxidant antinociceptive antitumor leishmanicidal processes bites others use profile 2 1998 (199 2021 research 3 199 (19 202 19 (1 20 1 (

This work describes the synthesis of new 1,3-benzoxathiol-2-one sulfonamides and evaluation of their ability to inhibit some in vitro (coagulant, proteolytic and hemolytic) and in vivo (hemorrhagic, edematogenic and lethality) toxic activities of Bothrops jararaca and Bothrops jararacussu venoms. Compounds have been synthesized from the coupling of intermediate 5-amino-6 methoxybenzo[d][1,3]oxathiol-2-one 4 with benzenesulfonyl chlorides. Characterization of the products was achieved by nuclear magnetic resonance (NMR) and electrospray ionization mass spectra (ESI-MS) techniques. Biological assay results have shown that most of compounds inhibited the main toxic activities of the venom of the two snake species. Compound 5b (N-(6 methoxy-2 oxobenzo[d][1,3]oxathiol-5-yl)-4-nitrobenzenesulfonamide) was the most efficient in inhibiting hemolysis of B. jararaca, and coagulation and proteolysis induced by both venoms. For in vivo activities, all compounds inhibited the edema, from 35 to 72%, and most of them exhibited antihemorrhagic and antilethality activities. Thus, the results pointed to the biological potential of these compounds, being promising molecules to treat envenomation by these snakes as well as to aid the current antivenom serum therapy.

Abstract Background: Cnidarians produce toxins, which are composed of different polypeptides that induce pharmacological effects of biotechnological interest, such as antitumor, antiophidic and anti-clotting activities. This study aimed to evaluate toxicological activities and potential as antitumor and antiophidic agents contained in total extracts from five cnidarians: Millepora alcicornis, Stichodactyla helianthus, Plexaura homomalla, Bartholomea annulata and Condylactis gigantea (total and body wall). Methods: The cnidarian extracts were evaluated by electrophoresis and for their phospholipase, proteolytic, hemorrhagic, coagulant, fibrinogenolytic, neuromuscular blocking, muscle-damaging, edema-inducing and cytotoxic activities. Results: All cnidarian extracts showed indirect hemolytic activity, but only S. helianthus induced direct hemolysis and neurotoxic effect. However, the hydrolysis of NBD-PC, a PLA2 substrate, was presented only by the C gigantea (body wall) and S. helianthus. The extracts from P. homomalla and S. helianthus induced edema, while only C gigantea and S. helianthus showed intensified myotoxic activity. The proteolytic activity upon casein and fibrinogen was presented mainly by B. annulata extract and all were unable to induce hemorrhage or fibrinogen coagulation. Cnidarian extracts were able to neutralize clotting induced by Bothrops jararacussu snake venom, except M. alcicornis. All cnidarian extracts were able to inhibit hemorrhagic activity induced by Bothrops moojeni venom. Only the C. gigantea (body wall) inhibited thrombin-induced coagulation. All cnidarian extracts showed antitumor effect against Jurkat cells, of which C. gigantea (body wall) and S. helianthus were the most active; however, only C. gigantea (body wall) and M. alcicornis were active against B16F10 cells. Conclusion: The cnidarian extracts analyzed showed relevant in vitro inhibitory potential over the activities induced by Bothrops venoms; these results may contribute to elucidate the possible mechanisms of interaction between cnidarian extracts and snake venoms.

The ability of crude extracts of the brown seaweed Spatoglossum schröederi to counteract some of the biological activities of Lachesis muta snake venom was evaluated. In vitro assays showed that only the extract of S. schröederi prepared in ethyl acetate was able to inhibit the clotting of fibrinogen induced by L. muta venom. On the other hand, all extracts were able to inhibit partially the hemolysis caused by venom and those prepared in dichloromethane or ethyl acetate fully neutralized the proteolysis and hemorrhage produced by the venom. Moreover, the dichloromethane or ethyl acetate extracts inhibited the hemolysis induced by an isolated phospholipase A2 from L. muta venom, called LM-PLA2-I. In contrast, the hexane extract failed to protect mice from hemorrhage or to inhibit proteolysis and clotting. These results show that the polarity of the solvent used to prepare the extracts of S. schröederi algae influenced the potency of the inhibitory effect of the biological activities induced by L. muta venom. Thus, the seaweed S. schröederi may be a promising source of natural inhibitors of the enzymes involved in biological activities of L. muta venom.

The effect of a Brazilian algae extract and also a mixture of two secodolastane diterpenes (linearol/isolinearol) that were isolated from the marine brown alga Canistrocarpus cervicornis were evaluated against biological activities of Lachesis muta snake venom. In vitro assays showed that the crude extract and the diterpenes were able to inhibit the clotting and proteolytic activity induced by L. muta crude venom, but not the hemolytic activity. However, only the diterpenes inhibited the hemolysis caused by a purified phospholipase A2 previously isolated from L. muta venom, denoted LM-PLA2-I. Interestingly, the crude algal extract and the diterpenes were able to protect mice from hemorrhage induced by L. muta venom. Thus, we may conclude that marine algae are rich and powerful sources of molecules that may be used against L. muta accidents in order to improve treatment of envenomation by this snake.