Alisson Meza Novais
@ufam.edu.br
Chemistry Department
RESEARCH, TEACHING, or OTHER INTERESTS
Organic Chemistry
Scopus Publications
- Straightforward synthesis of cytosporone analogs AMS35AA and AMS35BB
NEIMAR VITOR, ALISSON MEZA, ROBERTO S. GOMES, JAMAL RAFIQUE, DÊNIS P. DE LIMA, ADILSON BEATRIZ
Anais Da Academia Brasileira De Ciencias, 2021
Cytosporones, a class of octaketide resorcinolic lipids, have drawn the attention of researchers for exhibiting a number of notable biological properties. Herein, we describe routes to synthesize the bioactive synthetic resorcinolic lipids AMS35AA and AMS35BB with excellent overall yields using 3,5-dimethoxybenzoic acid as the starting material. The methods proved remarkably efficient to achieve the target compounds and comprise the synthesis of AMS35AA catalyzed by ascorbic acid (vitamin C). - Effects of 3-Heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one alone or/in association with cyclophosphamide on testicular function
Rodrigo Juliano Oliveira, Andréa Luiza Cunha‐Laura, Caroline Amélia Gonçalves, Antônio Carlos Duenhas Monreal, Deiler Sampaio Costa, Alisson Meza, Dênis Pires Lima, Adilson Beatriz, Ernani Aloysio Amaral, Sarah Alves Auharek
Andrologia, 2020
Chemotherapy for cancer treatment may result in a temporary or long-term gonadal damage resulting in subfertility or infertility. Cyclophosphamide (CY) is a cytotoxic alkylating agent that has been widely used in the treatment of cancer. Recent studies have shown that synthetic resorcinol lipid AMS35AA (3-Heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one) may be an important adjuvant chemotherapy that potentiates mutagenic damage and increases apoptosis caused by CY. The present study investigates the action of AMS35AA alone or/in association with CY on testicular function. Animals were divided into four groups: (a) control group: received only water; (b) CY group: received 150 μg/g of CY b.w., i.p.; (c) AMS35AA group: received 10 μg/g of AMS35AA b.w., i.p; and (d) associated group: received 10 μg/g of AMS35AA + 150 μg/g of CY b.w., i.p. Four weeks after the treatment, the results showed that testes weight of CY and associated groups decreased. However, the number of Sertoli cell and Leydig cell per testis was similar in control and treated groups. Our findings provide strong evidence that the AMS35AA alone or in CY association is not toxic to spermatogenesis. The absence of toxicity of AMS35AA supports the view that the resorcinolic lipid could be used associated with CY chemotherapy without causing adverse effects to testes function. - A straightforward method for synthesizing bioactive resorcinolic lipid analogues
Denilson Silva Dos Santos, Alisson Meza, Roberto Da Silva Gomes, Denis Pires De Lima, Adilson Beatriz
Orbital, 2020
Neste trabalho, foi planejada a síntese de lipídeos resorcinólicos análogos as citosporonas utilizando métodos clássicos de síntese orgânica. O objetivo principal foi à preparação dos compostos: ácido 2,4-dihidróxi-6-octil-benzóico (<strong>6</strong>) e 2,4-diidróxi-6-(8-oxooctil)-benzóico (<strong>7</strong>). Foram estudadas rotas de síntese visando à produção desses compostos, foi possível obtenção de três intermediários avançados, com sucesso: 2,4 dimetóxi-6-octil-benzoato de etila (<strong>8</strong>), 2-hidróxi-4-metóxi-6-octil-benzoato de etila (<strong>9</strong>) e ácido 2-hidróxi-4-metóxi-6-octil-benzóico (<strong>10</strong>), os quais tiveram suas estruturas determinadas por técnicas de espectroscopia de RMN de <sup>1</sup>H e de <sup>13</sup>C, e no caso de (<strong>10</strong>) incluindo técnicas bidimensionais (HSQC e HMBC). - Synthesis and antioxidant and antimicrobial properties of β-hydroxy sulfides, sulfoxides, and sulfones derived from cardanol and glycerol derivatives
Suély Copini, Ana Micheletti, Dênis de Lima, Roberto Gomes, Alisson Meza, Adilson Beatriz
Journal of the Brazilian Chemical Society, 2020
Natural and synthetic sulfur-bearing organic compounds have many applications in medicinal chemistry. This article reports the preparation of amphiphilic -hydroxy sulfides, sulfoxides, and sulfones derived from cardanol and glycerol. Thiolysis of cardanol epoxide 3 with various thiols (4a-4j) in ethanol or water yielded the corresponding -hydroxy sulfides 5a-5j (61-95%). Treatment with 30% H 2 O 2 in acetic acid at ambient temperature completely converted these products into -hydroxy sulfoxides 6a-6j and sulfones 7a, 7c-7f, 7h-7j. The synthesized compounds were characterized by 1 H nuclear magnetic resonance (NMR), 13 C NMR, high-resolution mass spectroscopy (HRMS) and performed the in vitro evaluation antimicrobial activities against standard strains of Staphylococcus aureus and Escherichia coli. Compounds 5a, 5d-5f, and 5h-5j proved moderately active against S. aureus. None of the compounds were active against E. coli. -Hydroxy-sulfides 5a-5j were also evaluated for antioxidant properties but failed to exhibit significant activity. - Resorcinolic lipid 3-heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one is a strategy for melanoma treatment
Stephanie Dynczuki Navarro, Lucas Roberto Pessatto, Alisson Meza, Edwin José Torres de Oliveira, Sarah Alves Auharek, Lizia Colares Vilela, Dênis Pires de Lima, Ricardo Bentes de Azevedo, Candida Aparecida Leite Kassuya, Osmar Ignacio Ayala Cáceres, Roberto da Silva Gomes, Adilson Beatriz, Rodrigo Juliano Oliveira, Marco Antonio Utrera Martines
Life Sciences, 2018 - Evaluation of the antitumor potential of the resorcinolic lipid 3-heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one in breast cancer cells
ANA PAULA MALUF RABACOW, ALISSON MEZA, EDWIN JOSÉ TORRES DE OLIVEIRA, NATAN DE DAVID, NEIMAR VITOR, ANDRÉIA CONCEIÇÃO MILAN BROCHADO ANTONIOLLI-SILVA, MARIA DE FÁTIMA CEPA MATOS, RENATA TRENTIM PERDOMO, ROBERTO DA SILVA GOMES, DÊNIS PIRES DE LIMA, ADILSON BEATRIZ, RODRIGO JULIANO OLIVEIRA
Anticancer Research, 2018
Background/Aim: In recent years, the search for new anticancer experimental agents derived from natural products or synthetic analogues, such as resorcinolic lipids, has received increased attention. The present study aimed to evaluate the antitumor potential, describe the cell death mechanism and the effects of 3-Heptyl-3,4,6-trimethoxy-3Hisobenzofuran-1-one (AMS35AA) in combination with different chemotherapeutic agents in the MCF-7 cell line. Materials and Methods: Analysis of cytotoxic, genotoxic, membrane integrity, cell death and gene expression induced by the compound was performed. Results: The AMS35AA and its association with 5-FU demonstrated reduction of cell viability; increase of cell death; enhancement of genomic damage and accumulation of cells in G<sub>2</sub>/M phase. Conclusion: AMS35AA has potential for breast cancer treatment since it is capable of exerting cytotoxic and cytostatic effects in a breast cell line and also could be an adjuvant in cancer therapy when combined with 5-FU. - In Vivo chemotherapeutic insight of a novel isocoumarin (3-hexyl-5,7-dimethoxy-isochromen-1-one): Genotoxicity, cell death induction, leukometry and phagocytic evaluation
Flávio Henrique Souza de Araújo, Débora Rojas de Figueiredo, Sarah Alves Auharek, João Renato Pesarini, Alisson Meza, Roberto da Silva Gomes, Antônio Carlos Duenhas Monreal, Andréia Conceição Milan Brochado Antoniolli-Silva, Dênis Pires de Lima, Candida Aparecida Leite Kassuya, Adilson Beatriz, Rodrigo Juliano Oliveira
Genetics and Molecular Biology, 2017
Chemotherapy is one of the major approaches for the treatment of cancer. Therefore, the development of new chemotherapy drugs is an important aspect of medicinal chemistry. Chemotherapeutic agents include isocoumarins, which are privileged structures with potential antitumoral activity. Herein, a new 3-substituted isocoumarin was synthesized from 2-iodo-3,5-dimethoxy-benzoic acid and oct-1-yne in a cross-coupling Sonogashira reaction followed by a copper iodide-catalyzed intramolecular cyclization as key step using MeOH/Et3N as the solvent system. The present study also evaluated the leukometry, phagocytic activity, genotoxic potential and cell death induction of three different doses (5 mg/kg, 10 mg/kg and 20 mg/kg) of this newly synthesized isocoumarin, alone and in combination with the commercial chemotherapeutic agents cyclophosphamide (100 mg/kg) and cisplatin (6 mg/kg) in male Swiss mice. The results suggest that the isocoumarin has genotoxicity and causes cell death. Noteworthy, this new compound can increase splenic phagocytosis and lymphocyte frequency, which are related to immunomodulatory activity. When combined with either cyclophosphamide or cisplatin, chemopreventive activity led to a reduction in the effects of both chemotherapeutic drugs. Thus, the new isocoumarin is not a candidate for chemotherapeutic adjuvant in treatments using cyclophosphamide or cisplatin. Nevertheless, the compound itself is an important prototype for the development of new antitumor drugs. - Cardanol: Toxicogenetic assessment and its effects when combined with cyclophosphamide
Beatriz Ursinos Catelan Schneider, Alisson Meza, Adilson Beatriz, João Renato Pesarini, Pamela Castilho de Carvalho, Mariana de Oliveira Mauro, Caroline Bilhar Karaziack, Andréa Luiza Cunha-Laura, Antônio Carlos Duenhas Monreal, Renata Matuo, Dênis Pires de Lima, Rodrigo Juliano Oliveira
Genetics and Molecular Biology, 2016
Cardanol is an effective antioxidant and is a compound with antimutagenic and antitumoral activity. Here, we evaluated the genotoxic and mutagenic potential of saturated side chain cardanol and its effects in combination with cyclophosphamide in preventing DNA damage, apoptosis, and immunomodulation. Swiss mice were treated with cardanol (2.5, 5 and 10 mg/kg) alone or in combination with cyclophosphamide (100 mg/kg). The results showed that cardanol is an effective chemopreventive compound, with damage reduction percentages that ranged from 18.9 to 31.76% in the comet assay and from 45 to 97% in the micronucleus assay. Moreover, cardanol has the ability to reduce the frequency of apoptosis induced by cyclophosphamide. The compound did not show immunomodulatory activity. A final interpretation of the data showed that, despite its chemoprotective capacity, cardanol has a tendency to induce DNA damage. Hence, caution is needed if this compound is used as a chemopreventive agent. Also, this compound is likely not suitable as an adjuvant in chemotherapy treatments that use cyclophosphamide. - Cytosporones and related compounds, a review: Isolation, biosynthesis, synthesis and biological activity of promising fungal resorcinolic lipids
Alisson Meza, Edson Anjos dos Santos, Roberto Silva Gomes, Dênis de Lima, Adilson Beatriz
Current Organic Synthesis, 2015
Phenolic lipids constitute a class of bioactive compounds comprising molecules having hydrophobic tails linked to a phenolic polar head, widely distributed in nature, with great variety of biological and industrial potential. The cytosporones, which are octaketide phenolic lipids, have been attracting the attention of many researchers owing to their biological potential, such as fungicidal, allelopathic, bactericidal and, cytotoxic activities. In 2008, it was noticed that the so-called cytosporone B specifically binds to the ligand-binding domain of Nur77 or TR3, and is a potent killer in agonist stimuli. Some research groups are constantly striving to synthesize cytosporones and, many works have been published since 2003. Recently, some new similar octaketides were isolated and a few synthetic approaches are reported in the literature. Many results point out that cytosporones are potential molecules to develop promising pharmaceutical and agrochemical agents. Keywords: Allelopathy, anticancer, antimicrobials, dothiorelones, endophytic fungi, Nur77, polyketide. - A novel cytosporone 3-Heptyl-4,6-dihydroxy-3H-isobenzofuran-1-one: Synthesis; toxicological, apoptotic and immunomodulatory properties; and potentiation of mutagenic damage
Rodrigo Juliano Oliveira, Stephanie Dynczuki Navarro, Dênis Pires de Lima, Alisson Meza, João Renato Pesarini, Roberto da Silva Gomes, Caroline Bilhar Karaziack, Mariana de Oliveira Mauro, Andréa Luiza Cunha-Laura, Antônio Carlos Duenhas Monreal, Wanderson Romão, Valdemar Lacerda Júnior, Adilson Beatriz
BMC Cancer, 2015
BACKGROUND: A large number of studies are attempting to identify alternative products from natural sources or synthesized compounds that effectively interact with cancer cells without causing adverse effects on healthy cells. Resorcinolic lipids are a class of bioactive compounds that possess anticancer activity and are able to interact with the lipid bilayer. Therefore, the objective of this study was to synthesize a novel resorcinolic lipid and test its biological proprieties. METHODS: We aimed to synthesize a novel resorcinolic lipid belonging to the class of cytosporones, AMS049 (3-Heptyl-4,6-dihydroxy-3H-isobenzofuran-1-one) and to evaluate the toxicity of two concentrations of this lipid (7.5 and 10 mg/kg) by determining its genotoxic, mutagenic, immunomodulatory, and apoptotic effects, as well as any biochemical and histopathological alterations in mice treated with cyclophosphamide. The results were analyzed by ANOVA followed by the Tukey test A . level of significance of p < 0.05 was adopted. RESULTS: The new cytosporone AMS049 was synthesized in only three steps and in satisfactory yields. The results indicate that the compound is neither genotoxic nor mutagenic and does not alter biochemical parameters. The histological alterations observed in the liver and kidneys did not compromise the function of these organs. Histology of the spleen suggested immunomodulation, although no changes were observed in splenic phagocytosis or differential blood cell count. The results also show that AMS049 potentiates the mutagenic effect of the chemotherapy drug cyclophosphamide and that the combination induces apoptosis. CONCLUSION: These facts indicate a potential therapeutic application of this novel cytosporone as an important chemotherapeutic adjuvant. - A new synthetic resorcinolic lipid 3-Heptyl-3,4,6-trimethoxy-3H- isobenzofuran-1-one: Evaluation of toxicology and ability to potentiate the mutagenic and apoptotic effects of cyclophosphamide
Stephanie Dynczuki Navarro, Adilson Beatriz, Alisson Meza, João Renato Pesarini, Roberto da Silva Gomes, Caroline Bilhar Karaziack, Andréa Luiza Cunha-Laura, Antônio Carlos Duenhas Monreal, Wanderson Romão, Valdemar Lacerda Júnior, Mariana de Oliveira Mauro, Rodrigo Juliano Oliveira
European Journal of Medicinal Chemistry, 2014 - Total synthesis and allelopathic activity of cytosporones A-C
Charles E. M. Zamberlam, Alisson Meza, Carla Braga Leite, Maria Rita Marques, Dênis P. de Lima, Adilson Beatriz
Journal of the Brazilian Chemical Society, 2012
