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2 results on '"Chermont S"'

1. Synthesis and evaluation of the mutagenicity of 3-alkylpyridine marine alkaloid analogues with anticancer potential.

Author

Barbosa MCS, de Souza Barbosa C, de Oliveira JT, Moreira NCS, de Miranda Martins NR, Alves Gomes GK, Caldeira CA, Alves E Costa ML, Martins Guimarães DS, Guimarães L, Nascimento CS Jr, de Pilla Varotti F, Ribeiro Viana GH, and Santos FVD

Subjects
Alkaloids chemical synthesis, Alkaloids chemistry, Animals, Antimalarials chemical synthesis, Antimalarials chemistry, Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Comet Assay, Humans, Inhibitory Concentration 50, Micronucleus Tests, Models, Molecular, Plasmodium falciparum drug effects, Pyridines chemical synthesis, Pyridines chemistry, Structure-Activity Relationship, Alkaloids pharmacology, Antimalarials pharmacology, Antineoplastic Agents pharmacology, Pyridines pharmacology, Theonella chemistry
Abstract

Theonella sp is an important source of biologically-active 3-alkylpyridine alkaloids (3-APAs) that has shown a wide variety of promising biological effects. In the present work, two new 3-APAs analogues were synthesized based on molecular modeling studies to act as potential antimalarial agents. These theoneladin C analogues, containing the thiocyanate group in their chemical structures, were synthesized and evaluated against Plasmodium falciparum (IC 50 values ranging from 2.3 to 5.5μM). The structural and energetic analysis demonstrated a high chemical affinity of the two analogues for their target, the heme group. However, despite the good antimalarial activity, the compounds exhibited high cytotoxicity and a lack of selectivity for human cell lines. These findings prompted us to evaluate the cytotoxicity of these compounds against human cancer cell lines. In order to better understand the mechanisms responsible for the toxicity, a variety of genotoxicity assays were performed in vitro. One of the compounds assayed presented an interesting selectivity and high toxicity to the human colon cancer cell line RKO-AS45-1. In addition, the results of the micronucleus assay, comet assay, Ames assay and annexin-V/propidium iodide staining showed that the synthetic alkaloids were able to induce chromosomal mis-segregation and trigger cell death by apoptosis. These results demonstrate that the compounds assessed herein may be promising prototypes of anticancer chemotherapeutic agents., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Published
2018
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2. Synthesis and evaluation of the mutagenicity of 3-alkylpyridine marine alkaloid analogues with anticancer potential

Author

Gustavo Henrique Ribeiro Viana, Natália Rezende de Miranda Martins, Maria Cristina Da Silva Barbosa, Marília Ladeira Alves e Costa, Clebio S. Nascimento, Natália Chermont S. Moreira, Júlia Teixeira de Oliveira, Camila A. Caldeira, Fernando de Pilla Varotti, Daniel Silqueira Martins Guimarães, Fábio Vieira dos Santos, Gabrielle Kéfrem Alves Gomes, Camila de Souza Barbosa, and Luciana Guimarães

Subjects
0301 basic medicine, Models, Molecular, Cell Survival, Pyridines, Health, Toxicology and Mutagenesis, Plasmodium falciparum, Antineoplastic Agents, Biology, Pharmacology, medicine.disease_cause, Ames test, 03 medical and health sciences, chemistry.chemical_compound, Antimalarials, Inhibitory Concentration 50, Structure-Activity Relationship, Alkaloids, Cell Line, Tumor, Genetics, medicine, Structure–activity relationship, Animals, Humans, Propidium iodide, Cytotoxicity, Cell Proliferation, Micronucleus Tests, Cell growth, Alkaloid, Comet assay, 030104 developmental biology, Biochemistry, chemistry, Comet Assay, Theonella, Genotoxicity
Abstract

Theonella sp is an important source of biologically-active 3-alkylpyridine alkaloids (3-APAs) that has shown a wide variety of promising biological effects. In the present work, two new 3-APAs analogues were synthesized based on molecular modeling studies to act as potential antimalarial agents. These theoneladin C analogues, containing the thiocyanate group in their chemical structures, were synthesized and evaluated against Plasmodium falciparum (IC50 values ranging from 2.3 to 5.5μM). The structural and energetic analysis demonstrated a high chemical affinity of the two analogues for their target, the heme group. However, despite the good antimalarial activity, the compounds exhibited high cytotoxicity and a lack of selectivity for human cell lines. These findings prompted us to evaluate the cytotoxicity of these compounds against human cancer cell lines. In order to better understand the mechanisms responsible for the toxicity, a variety of genotoxicity assays were performed in vitro. One of the compounds assayed presented an interesting selectivity and high toxicity to the human colon cancer cell line RKO-AS45-1. In addition, the results of the micronucleus assay, comet assay, Ames assay and annexin-V/propidium iodide staining showed that the synthetic alkaloids were able to induce chromosomal mis-segregation and trigger cell death by apoptosis. These results demonstrate that the compounds assessed herein may be promising prototypes of anticancer chemotherapeutic agents.

Published
2017

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