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 (

Abstract Many biological activities are described for the Clusiaceae family. Clusia fluminensis, a species from Brazilian flora, is mainly employed for ornamental purposes. This review aimed to depict the current knowledge of C. fluminensis from a bioprospecting standpoint. “Clusia fluminensis” search term was applied in Scopus, Web of Science, PubMed and Bireme databases according to PRISMA-ScR statement. Selected papers on Phytochemistry or Bioactivity followed hand searching procedures. Bioactivity preclinical studies considered in vitro or in vivo biological systems, treated with plant extracts or isolated compounds. The outcomes were compared with standard or no treatment control groups. Critical appraisal of individual trials considered completeness in the research fields. Our results showed that 81% of the selected papers presented high level of completeness, 69% revealed phytochemical parameters and 31% biological applications of plant extracts and isolated compounds. Polyisoprenylated benzophenones, terpenoids, sterols and phenolic compounds were identified. Antiviral, insecticidal and snake antivenom activities were reported. In conclusion, the phytochemical data reinforce the reported activities. Potential applications in personal care, nutritional supplementation and pharmaceutical, food, chemical or textile industries were also identified. Toxicological and phytochemical complementary studies may be required. family flora purposes C standpoint Scopus Science PRISMAScR PRISMA ScR statement procedures systems groups fields 81 69 31 benzophenones terpenoids identified Antiviral conclusion care pharmaceutical food required 8 6 3

Abstract Access to genetic resources (GR) and/or traditional knowledge associated with genetic resources (ATK) has been regulated in Brazil since 2001. The law 13,123 / 2015 determined a significant change in the theme, mainly on the rules of distribution of benefits obtained for conservation and sustainable use of biodiversity, the access to technology and technology transfer, the exploitation of products or reproductive material from the GR or ATK and consignment to the outside of part or all the living or dead organism shipped for GR. The implementation of international treaties on GR and ATK for research, biotechnological development and bioprospecting have been causing difficulties for Brazilian researchers, mainly due to the lack of information and dissemination available for compliance with the legislation. In this work, the members of the Committee for Access to Genetic Resources and Associated Traditional Knowledge of the Federal Fluminense University (UFFGEN) - Brazil, and collaborators performed a critical reflection on the new law, helping Brazilian researchers with information necessary to understand the changes made by the new legislation, especially in the field of Biotechnology associated with Brazilian Biodiversity.

ABSTRACT Plants represent a huge source of substances, with pharmacological potential. Brazil has a diversity of agricultural insect pests and an urgent need for safer methods of insect control. Dysdercus peruvianus (Guerin-Meneville, 1831), Pyrrhocoridae, is an economically important species of the Order Hemiptera and a pest of cotton (Gossypium hirsutum L., Malvaceae). Secondary metabolites in stems of Clusia hilariana Schltdl., Clusiaceae, such as terpenes and benzophenones, have been reported to be insecticidal. The present study investigated the effects of semi-purified fractions of hexane crude extracts from male C. hilariana stems on development of D. peruvianus. Biological parameters at different stages of development including body malformations, range of molting period and toxicity were evaluated. Most insects died and failed to develop due to attachment of their exuviae to the abdomen. Deformations of wings and defective tarsi also occurred. The secondary metabolites from semi-purified fractions of C. hilariana caused mortality, interference in molting and metamorphosis, and body deformations, probably by interacting with the neuroendocrine system. The results demonstrate the potential of C. hilariana extracts as an alternative for the control of the phytophagous insect D. peruvianus and for the development of environmentally safe and biodegradable bio insecticides.

ABSTRACT This study aims the anatomical description and chemical characterization of aerial parts of Clusia criuva Cambess., Clusiaceae in addition to the evaluation of the antioxidant activity of crude extracts, correlated to the flavonoid content. The morphological characterization was performed using traditional techniques of plant anatomy. For phytochemical studies, crude extracts were obtained by static maceration and analyzed by thin layer chromatography. The antioxidant activity and the flavonoids content were determined by colorimetric methods involving, respectively, 2,2-diphenyl-1-picrylhydrazyl free radical and aluminum chloride. C. criuva has uniseriate epidermis, paracytic stomata, hypostomatic leaves, cuticular flanges and cordiform vascular cylinder with accessory bundles. Chemical prospecting confirmed the abundant presence of terpenes and phenols in the extracts of leaves and of fruits. The methanolic extract of seeds showed the lowest EC50 value, but the methanolic extract of pericarps exhibited the highest maximum antioxidant activity. The results suggested a high percentage of flavonoids in the hexanic extract of pericarps, however, this could represent, in fact, the presence of benzophenones. Secretory ducts and the shape of the midrib are diagnostic for C. criuva. The antioxidant activity is not directly related to the flavonoids. The results indicate the importance of future studies with C. criuva chemical constituents.

ABSTRACT The effects of the hexanic extracts of the fruits and flowers of Clusia fluminensis Planch. & Triana, Clusiaceae, as well as their main constituents, the triterpene lanosterol and the benzophenone clusianone, were evaluated on hemipterans Dysdercus peruvianus and Oncopeltus fasciatus. The topical treatments of insects with the hexanic extracts significantly affected the survival of O. fasciatus, but not that of D. peruvianus. Concomitantly, extracts delayed the development of both hemipterans. Moreover, isolated lanosterol significantly reduced both the survival and development of O. fasciatus and D. peruvianus, while clusianone only reduce the survival of D. peruvianus and marginally inhibited the development of both insects. The results show the specific activity of lanosterol and clusianone against the two evaluated insect species and indicate the potential of compounds derived from C. fluminensis for the development of specific biopesticides for the control of agricultural pests. Subsequent work will examine the mode of action of lanosterol and clusianone isolates from C. fluminensis.

Studies evaluated the effects of hexanic extracts from the fruits and flowers of Clusia fluminensis and the main component of the flower extract, a purified benzophenone (clusianone), against Aedes aegypti. The treatment of larvae with the crude fruit or flower extracts from C. fluminensis did not affect the survival of Ae. aegypti (50 mg/L), however, the flower extracts significantly delayed development of Ae. aegypti. In contrast, the clusianone (50 mg/L) isolate from the flower extract, representing 54.85% of this sample composition, showed a highly significant inhibition of survival, killing 93.3% of the larvae and completely blocking development of Ae. aegypti. The results showed, for the first time, high activity of clusianone against Ae. aegypti that both killed and inhibited mosquito development. Therefore, clusianone has potential for development as a biopesticide for controlling insect vectors of tropical diseases. Future work will elucidate the mode of action of clusianone isolated from C. fluminensis.

Derivados de benzofenonas despertam grande interesse científico. A família Clusiaceae é conhecida por produzir grandes quantidades dessas substâncias, com vários resíduos isoprênicos em suas estruturas, os quais são responsáveis pela complexidade e variedade estrutural observada nesta classe de substâncias, e também contribuem para suas atividades biológicas. Clusia é um gênero importante pertencente à família Clusiaceae, com 55 benzofenonas poliisopreniladas diferentes identificadas até o momento. Essas substâncias foram analisadas sob perspectivas biossintéticas e quimiossistemáticas, permitindo determinar características relacionadas à sua produção, acumulação e distribuição dentro desse gênero. As benzofenonas poliisopreniladas encontradas em Clusia apresentaram um grau elevado de prenilação, com 2 a 5 unidades isoprênicas e uma maior ocorrência em flores e frutos. A seção Cordylandra mostrou uma ocorrência muito semelhante de derivados de 2,4,6-triidroxibenzofenona e biciclo[3.3.1]nonano-2,4,9-triona, a maioria deles com 4 unidades isoprênicas. Na seção Anandrogyne predominam derivados de 2,4,6-triidroxibenzofenona com 2 unidades isoprênicas, e em Chlamydoclusia predominam os derivados de biciclo[3.3.1]nonano-2,4,9-triona com 4 unidades isoprênicas. Embora altamente preniladas, essas substâncias mostraram índices de oxidação baixos, o que, sob uma perspectiva evolucionária, corrobora o fato de que Clusiaceae é uma família em transição, com alguns aspectos comuns tanto à famílias botânicas basais, quanto derivadas.

Benzophenone derivatives are special metabolites that arouse great scientific interest. The Clusiaceae family is known for producing large amounts of benzophenone derivatives with several isoprene residues on their structures, which are responsible for the observed complexity and structural variety in this class of substances, and also contribute to their biological activities. Clusia is an important genus belonging to Clusiaceae, with 55 different polyisoprenylated benzophenones identified so far. These substances were analyzed from biosynthetic and chemosystematic points of view, allowing the determination of characteristics regarding their production, accumulation and distribution within this genus. Polyisoprenylated benzophenones found in Clusiashowed a high prenylation degree, with 2 to 5 isoprene units and a greater occurrence in flowers and fruits. Section Cordylandra showed a very similar occurrence of 2,4,6-trihydroxybenzophenone derivatives and bicyclo[3.3.1]nonane-2,4,9-trione derivatives, the majority of them with 4 isoprene units. In section Anandrogyne there is a predominance of simple 2,4,6-trihydroxy-benzophenone derivatives, with 2 isoprene units, and in Chlamydoclusia predominates bicyclo[3.3.1]nonane-2,4,9-trione derivatives with 4 isoprene units. Although highly prenylated, these substances showed low oxidation indexes, which from an evolutionary perspective corroborates the fact that Clusiaceae is a family in transition, with some common aspects with both basal and derived botanical families.

Clusia fluminensis Planch. & Triana (Clusiaceae Lindl.) é uma espécie nativa encontrada em regiões de alta luminosidade e restrição hídrica. O objetivo deste estudo foi avaliar a atividade antioxidante dos extratos brutos de Clusia fluminensis através do sequestro do radical livre estável DPPH, e a determinação do conteúdo de flavonas e flavonóis nesses extratos. O extrato acetônico dos frutos apresentou o menor valor de EC50 (2,71 ± 0,34 g extrato / g DPPH), o menor percentual de DPPH remanescente nas concentrações de 125 e 250 µg/mL (aproximadamente 4% em ambos), e também o maior percentual de flavonas e flavonóis (13,93 ± 0,21 %). Análise estatística sugere uma correlação positiva entre a presença de flavonóides e a atividade antioxidante do extrato. A partir dos resultados obtidos pode ser sugerido que o extrato acetônico dos frutos de C. fluminensis é um alvo interessante para a busca de substâncias com atividade antioxidante, especialmente flavonóides.

Clusia fluminensis Planch. & Triana (Clusiaceae Lindl.) is a native species found in regions of high luminosity and water restriction. The aim of this study was to evaluate the antioxidant activity of Clusia fluminensis crude extracts through the scavenging of the stable free radical DPPH, and the determination of flavones and flavonols content in these extracts. The fruit acetonic extract showed the lowest EC50 value (2.71 ± 0.34 g extract / g DPPH), the lowest percentage of remaining DPPH at the concentrations of 125 and 250 µg/mL (about 4% in both), and also the greatest percentage of flavones and flavonols (13.93 ± 0.21 %). Statistical analysis suggests a positive correlation between the presence of flavonoids and the antioxidant activity of this extract. From the obtained results it can be inferred that the acetonic extract of C. fluminensis fruits is an interesting target for the search of substances with antioxidant activity, especially flavonoids.

Plumbago scandens L. é uma espécie brasileira tropical/subtropical que ocorre ao longo da costa. Quimicamente, é principalmente representada por naftoquinonas, flavonóides, terpenóides e esteróides. objetivo do presente trabalho é estudar mudanças quantitativas da produção metabólica nas raízes de Plumbago scandens durante diferentes estágios de desenvolvimento fisiológico, relativos à floração. Os resultados indicaram a presença de quatro substâncias nos extratos: plumbagina, epi-isoshinanolona, ácido palmítico e sitosterol, independente do estágio de desenvolvimento. A naftoquinona plumbagina tem sempre mostrado ser o componente majoritário de todos os extratos. Naftoquinonas exibiram seus maiores conteúdos durante a floração, enquanto o conteúdo dos dois outros componentes decresceu durante este estágio, revelando um perfil inverso. A composição química modificou dependendo das necessidades da planta.

Plumbago scandens L. is a Brazilian tropical/subtropical species that occurs along the coast. Chemically it is mainly represented by naphthoquinones, flavonoids, terpenoids and steroids. The aim of the present work is to study quantitative changes in the root metabolic production of Plumbago scandens during different physiologic developmental stages relative to floration. The results indicated the presence of four substances in the extracts: plumbagin, epi-isoshinanolone, palmitic acid and sitosterol, independent on developmental stage. The naphthoquinone plumbagin has always showed to be the major component of all extracts. Naphthoquinones exhibited their highest content during floration, while the content of the two others components decreased during this stage, revealing an inverse profile. The chemical composition changed depending on the plant requirements.

O gênero Plumbago pertence à família Plumbaginaceae e apresenta uma variedade de atividades biológicas, a maioria atribuída à presença de naftoquinonas. Plumbagina é uma naftoquinona natural que pode ser obtida a partir de raízes de Plumbago scandens L. Na tentativa de descobrir a melhor técnica de extração dessa substância foram usadas, maceração estática, maceração dinâmica, extração com auxílio de ultrassom e extração em Soxhlet. Quatro substâncias foram detectadas qualitativamente: as naftoquinonas plumbagina e epi-isoshinanolona, o ácido palmítico e o sitosterol. Plumbagina foi sempre o componente majoritário em todos os extratos analisados e sua determinação quantitativa foi realizada através de cromatografia com fase gasosa acoplada à espectrometria de massas. A extração em Soxhlet foi a técnica mais eficiente para obtenção de plumbagina, entretanto a longa exposição a temperaturas elevadas favoreceu a degradação da plumbagina.

The Plumbago genus belongs to the Plumbaginaceae family and it is known due to its variety of biological uses, most of them attributed to the presence of naphthoquinones. Plumbagin is a naturally occurring naphthoquinone that can be obtained from roots of Plumbago scandens L. In order to find out the better technique for plumbagin extraction, were applied: static maceration, dynamic maceration, with assistance of ultrasonic waves and in Soxhlet apparatus. Four compounds were qualitatively detected in all extracts: the naphthoquinones plumbagin and epi-isoshinanolone, palmitic acid and sitosterol. Plumbagin was always the major component in all analyzed extracts and it was quantitatively determined by gas chromatograph coupled with mass spectrometer. Soxhlet was the most efficient extraction technique however, prolonged heating time promoted plumbagin degradation.