Dicentrine Purified from the Leaves of Ocotea puberula Controls the Intracellular Spread of L. (L.) amazonensis and L. (V.) braziliensis Amastigotes and Has Therapeutic Activity as a Topical Treatment in Experimental Cutaneous Leishmaniasis Jéssica Adriana Jesus, Gabriela Venicia Araujo Flores, Dalete Christine da Silva Souza, Daniela Costa Tristão, Dolores Remedios Serrano, et al. Microorganisms, 2025 Leishmaniasis, a complex disease caused by protozoal parasites of the genus Leishmania, presents various clinical forms, particularly a cutaneous clinical form. Treatment is typically performed with pentavalent antimonial and amphotericin B, both of which have severe side effects that hinder patient compliance. This emphasizes the need for the development of new, effective, and safe treatments. In this study, the leishmanicidal activity of the methanolic extract, an alkaloid-enriched fraction and dicentrine, the main alkaloid of the leaves of Ocotea puberula (Lauraceae), a native Brazilian plant traditionally used by the indigenous population to treat skin affections, was investigated in vitro. Additionally, an in vivo study evaluated the efficacy of a topical cream containing 0.5% dicentrine. The in vitro studies demonstrated high activity and selectivity of methanolic extract, alkaloid-enriched fraction, and dicentrine against the promastigote and amastigote forms of Leishmania (Leishmnia) amazonensis and Leishmania (Viannia) braziliensis. The leishmanicidal effect of dicentrine was related to the modulation of macrophage microbicidal activity. A cream containing 0.5% dicentrine showed high stability and, in permeation studies, dicentrine was retained in a skin-mimicking artificial membrane. This cream effectively inhibited the progression of the skin lesion in BALB/c mice infected with L. (L.) amazonensis, together with a reduced parasite number. Thus, dicentrine offers a promising alternative to the treatment of skin leishmaniasis.
Therapeutic Activity of a Topical Formulation Containing 8-Hydroxyquinoline for Cutaneous Leishmaniasis Sarah Kymberly Santos de Lima, Ítalo Novaes Cavallone, Dolores Remedios Serrano, Brayan J. Anaya, Aikaterini Lalatsa, et al. Pharmaceutics, 2023 Cutaneous leishmaniasis exhibits a wide spectrum of clinical manifestations; however, only a limited number of drugs are available and include Glucantime® and amphotericin B, which induce unacceptable side effects in patients, limiting their use. Thus, there is an urgent demand to develop a treatment for leishmaniasis. Recently, it was demonstrated that 8-hydroxyquinoline (8-HQ) showed significant leishmanicidal effects in vitro and in vivo. Based on that, this work aimed to develop a topical formulation containing 8-HQ and assess its activity in experimental cutaneous leishmaniasis. 8-HQ was formulated using a Beeler base at 1 and 2% and showed an emulsion size with a D50 of 25 and 51.3 µm, respectively, with a shear-thinning rheological behaviour. The creams were able to permeate artificial Strat-M membranes and excised porcine skin without causing any morphological changes in the porcine skin or murine skin tested. In BALB/c mice infected with L. (L.) amazonensis, topical treatment with creams containing 1 or 2% of 8-HQ was found to reduce the parasite burden and lesion size compared to infected controls with comparable efficacy to Glucantime® (50 mg/kg) administered at the site of the cutaneous lesion. In the histological section of the skin from infected controls, a diffuse inflammatory infiltrate with many heavily infected macrophages that were associated with areas of necrosis was observed. On the other hand, animals treated with both creams showed only moderate inflammatory infiltrate, characterised by few infected macrophages, while tissue necrosis was not observed. These histological characteristics in topically treated animals were associated with an increase in the amount of IFN-γ and a reduction in IL-4 levels. The topical use of 8-HQ was active in decreasing tissue parasitism and should therefore be considered an interesting alternative directed to the treatment of leishmaniasis, considering that this type of treatment is non-invasive, painless, and, importantly, does not require hospitalisation, improving patient compliance by allowing the treatment to be conducted.
Neolignans isolated from Saururus cernuus L. (Saururaceae) exhibit efficacy against Schistosoma mansoni Juliana R. Brito, Polrat Wilairatana, Daniel B. Roquini, Beatriz C. Parra, Marina M. Gonçalves, et al. Scientific Reports, 2022 Schistosomiasis, a parasitic disease caused by the blood fluke of the genus Schistosoma, affects over 230 million people, especially in developing countries. Despite the significant economic and public health consequences, only one drug is currently available for treatment of schistosomiasis, praziquantel. Thus, there is an urgent demand for new anthelmintic agents. Based on our continuous studies involving the chemical prospection of floristic biodiversity aiming to discover new bioactive compounds, this work reports the in vitro antiparasitic activity against Schistosoma mansoni adult worms of neolignans threo-austrobailignan-6 and verrucosin, both isolated from Saururus cernuus L. (Saururaceae). These neolignans showed a significant in vitro schistosomicidal activity, with EC50 values of 12.6–28.1 µM. Further analysis revealed a pronounced reduction in the number of S. mansoni eggs. Scanning electron microscopy analysis revealed morphological alterations when schistosomes were exposed to either threo-austrobailignan-6 or verrucosin. These relevant antischistosomal properties were accompanied by low cytotoxicity potential against the animal (Vero) and human (HaCaT) cell lines, resulting in a high selectivity index. Considering the promising chemical and biological properties of threo-austrobailignan-6 and verrucosin, this research should be of interest to those in the area of neglected diseases and in particular antischistosomal drug discovery.
N-(4-Methoxyphenyl)Pentanamide, a Simplified Derivative of Albendazole, Displays Anthelmintic Properties against the Nematode Toxocara canis Taís C. Silva, Ana C. Mengarda, Bruna L. Lemes, Susana A. Z. Lescano, Dalete Christine S. Souza, et al. Microbiology Spectrum, 2022 Infections caused by parasitic helminths have enormous health, social, and economic impacts worldwide. The treatment and control of these diseases have been dependent on a limited set of drugs, many of which have become less effective, necessitating the search for novel anthelmintic agents.
Simplified Derivatives of Dibenzylbutyrolactone Lignans from Hydrocotyle bonariensis as Antitrypanosomal Candidates Dalete Christine S. Souza, Thais A. Costa‐Silva, Thiago R. Morais, Juliana R. Brito, Edgard A. Ferreira, et al. Chemistry and Biodiversity, 2021 The search for the pharmacophore of a bioactive compound, crucial for drug discovery studies, involves the adequate arrangement of different atoms in the molecule. As part of a continuous work aiming discovery of new drug candidates against the protozoan parasite Trypanosoma cruzi, the hexane extract of Hydrocotyle bonariensis was subjected to a bioactivity‐guided fractionation to afford two chemically related dibenzylbutyrolactone lignans – hinokinin (1) and hibalactone (2). Compounds 1 and 2 showed activity against trypomastigote with EC50 values of 17.0 and 69.4 μM, respectively. Compound 1 was also active against the clinically relevant form of the parasite, amastigotes, displaying an EC50 value of 34.4 μM. The structure‐activity relationship (SAR) indicated that the absence of the double bond at C‐7 is a crucial feature for the increment of the antiparasitic activity. The lethal action of the most potent compound 1 was investigated in the trypomastigotes. The fluorescent‐based assay with SYTOX Green demonstrated a significant alteration of the plasma membrane permeability of the parasite. Additionally, compound 1 demonstrated no significant hemolytic activity in mice erythrocytes at 200 μM. To search the pharmacophore, three different simplified compounds – 3,4‐methylenedioxydihydrocinnamic acid (3), 3,4‐methylenedioxydihydrocinnamic alcohol (4) and 3,4‐methylenedioxycinnamic acid (5) – were prepared and tested against T. cruzi. These derivatives displayed EC50 values of 37.2 (3), 25.8 (4) and 73.5 (5) μM against trypomastigotes, and 41.3 (3) and 48.2 (4) μM against amastigotes, whereas compound 5 was inactive. Except for compound 2, which resulted in a CC50 value of 114.5 μM, all compounds showed no mammalian cytotoxicity at 200 μM. An in silico ADMET study was performed and predicted values demonstrated an acceptable drug‐likeness profile for compounds 1–5. Despite the minor reduction in the potency, the simplified derivatives retained the antitrypanosomal activity against the intracellular amastigotes, even with 95 % reduction of their molecular weight. Additionally, in silico studies suggested them as more soluble compounds, making these simplified structures promising scaffolds for optimization studies in Chagas disease.
RECENT SCHOLAR PUBLICATIONS
Activity–Selectivity of Flavonoid Derivatives in Endometriotic Cells KS Gomes, JA Coelho, PEH Tesser, DCS Souza, ML Silva, EA Ferreira, ... ACS omega 11 (6), 10703-10711 , 2026 2026 Citations: 1
Acetylene Acetogenin from Porcelia macrocarpa Exhibits Superior Efficacy against Schistosoma mansoni In Vivo DCS Souza, IA Brito, EA Oliveira, RA Cajás, TR Teixeira, J De Moraes, ... ACS omega 10 (50), 62036-62042 , 2025 2025
Chitosan Hydrogels Enriched with Biocompounds Extracted from Marine Sponges: Potential to Modulate the Inflammatory Process in an In Vitro Study M Bonifacio, CC Santi Martignago, DCS Souza, H Garcia-Motta, ... ACS omega 10 (24), 25605-25620 , 2025 2025 Citations: 4
Dicentrine Purified from the Leaves of Ocotea puberula Controls the Intracellular Spread of L. (L.) amazonensis and L. (V.) braziliensis Amastigotes and Has … JA Jesus, GV Araujo Flores, DCS Souza, DC Tristão, DR Serrano, ... Microorganisms 13 (2), 309 , 2025 2025
In vivo antischistosomal efficacy of Porcelia ponderosa γ-lactones DCS Souza, CH Totini, RA Cajás, TR Teixeira, EA Oliveira, ME Cirino, ... Phytomedicine 135, 156045 , 2024 2024 Citations: 11
Therapeutic activity of a topical formulation containing 8-hydroxyquinoline for cutaneous leishmaniasis SKS de Lima, ÍN Cavallone, DR Serrano, BJ Anaya, A Lalatsa, ... Pharmaceutics 15 (11), 2602 , 2023 2023 Citations: 9
Biseugenol from Ocotea cymbarum (Lauraceae) attenuates inflammation, angiogenesis and collagen deposition of sponge-induced fibrovascular tissue in mice BA Ferreira, FBR de Moura, KS Gomes, DC da Silva Souza, JHG Lago, ... Inflammopharmacology 31 (3), 1539-1549 , 2023 2023 Citations: 6
Flavonols, lignans and diacetylenes from leaves of Hydrocotyle leucocephala Cham. & Schltdl. and aerial parts of H. bonariensis Comm. ex Lam DCS Souza, GM Neves, LP Mello, LR Bertolin, GM Antar, OA Favero, ... Biochemical Systematics and Ecology 106, 104547 , 2023 2023 Citations: 3
Neolignans isolated from Saururus cernuus L. (Saururaceae) exhibit efficacy against Schistosoma mansoni JR Brito, P Wilairatana, DB Roquini, BC Parra, MM Gonçalves, ... Scientific Reports 12 (1), 19320 , 2022 2022 Citations: 27
N -(4-Methoxyphenyl)Pentanamide, a Simplified Derivative of Albendazole, Displays Anthelmintic Properties against the Nematode Toxocara canis TC Silva, AC Mengarda, BL Lemes, SAZ Lescano, DCS Souza, JHG Lago, ... Microbiology spectrum 10 (4), e01807-22 , 2022 2022 Citations: 14
Simplified Derivatives of Dibenzylbutyrolactone Lignans from Hydrocotyle bonariensis as Antitrypanosomal Candidates DCS Souza, TA Costa‐Silva, TR Morais, JR Brito, EA Ferreira, GM Antar, ... Chemistry & Biodiversity 18 (10), e2100515 , 2021 2021 Citations: 4
MOST CITED SCHOLAR PUBLICATIONS
Neolignans isolated from Saururus cernuus L. (Saururaceae) exhibit efficacy against Schistosoma mansoni JR Brito, P Wilairatana, DB Roquini, BC Parra, MM Gonçalves, ... Scientific Reports 12 (1), 19320 , 2022 2022 Citations: 27
N -(4-Methoxyphenyl)Pentanamide, a Simplified Derivative of Albendazole, Displays Anthelmintic Properties against the Nematode Toxocara canis TC Silva, AC Mengarda, BL Lemes, SAZ Lescano, DCS Souza, JHG Lago, ... Microbiology spectrum 10 (4), e01807-22 , 2022 2022 Citations: 14
In vivo antischistosomal efficacy of Porcelia ponderosa γ-lactones DCS Souza, CH Totini, RA Cajás, TR Teixeira, EA Oliveira, ME Cirino, ... Phytomedicine 135, 156045 , 2024 2024 Citations: 11
Therapeutic activity of a topical formulation containing 8-hydroxyquinoline for cutaneous leishmaniasis SKS de Lima, ÍN Cavallone, DR Serrano, BJ Anaya, A Lalatsa, ... Pharmaceutics 15 (11), 2602 , 2023 2023 Citations: 9
Biseugenol from Ocotea cymbarum (Lauraceae) attenuates inflammation, angiogenesis and collagen deposition of sponge-induced fibrovascular tissue in mice BA Ferreira, FBR de Moura, KS Gomes, DC da Silva Souza, JHG Lago, ... Inflammopharmacology 31 (3), 1539-1549 , 2023 2023 Citations: 6
Chitosan Hydrogels Enriched with Biocompounds Extracted from Marine Sponges: Potential to Modulate the Inflammatory Process in an In Vitro Study M Bonifacio, CC Santi Martignago, DCS Souza, H Garcia-Motta, ... ACS omega 10 (24), 25605-25620 , 2025 2025 Citations: 4
Simplified Derivatives of Dibenzylbutyrolactone Lignans from Hydrocotyle bonariensis as Antitrypanosomal Candidates DCS Souza, TA Costa‐Silva, TR Morais, JR Brito, EA Ferreira, GM Antar, ... Chemistry & Biodiversity 18 (10), e2100515 , 2021 2021 Citations: 4
Flavonols, lignans and diacetylenes from leaves of Hydrocotyle leucocephala Cham. & Schltdl. and aerial parts of H. bonariensis Comm. ex Lam DCS Souza, GM Neves, LP Mello, LR Bertolin, GM Antar, OA Favero, ... Biochemical Systematics and Ecology 106, 104547 , 2023 2023 Citations: 3
Activity–Selectivity of Flavonoid Derivatives in Endometriotic Cells KS Gomes, JA Coelho, PEH Tesser, DCS Souza, ML Silva, EA Ferreira, ... ACS omega 11 (6), 10703-10711 , 2026 2026 Citations: 1
Acetylene Acetogenin from Porcelia macrocarpa Exhibits Superior Efficacy against Schistosoma mansoni In Vivo DCS Souza, IA Brito, EA Oliveira, RA Cajás, TR Teixeira, J De Moraes, ... ACS omega 10 (50), 62036-62042 , 2025 2025
Dicentrine Purified from the Leaves of Ocotea puberula Controls the Intracellular Spread of L. (L.) amazonensis and L. (V.) braziliensis Amastigotes and Has … JA Jesus, GV Araujo Flores, DCS Souza, DC Tristão, DR Serrano, ... Microorganisms 13 (2), 309 , 2025 2025