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Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
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  3. Evaluation Of The In Vivo Acute Toxicity And In Vitro Genotoxicity And Mutagenicity Of Synthetic Β-carboline Alkaloids With Selective Cytotoxic Activity Against Ovarian And Breast Cancer Cell Lines.
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  3. Evaluation Of The In Vivo Acute Toxicity And In Vitro Genotoxicity And Mutagenicity Of Synthetic Β-carboline Alkaloids With Selective Cytotoxic Activity Against Ovarian And Breast Cancer Cell Lines.

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Evaluation of the in vivo acute toxicity and in vitro genotoxicity and mutagenicity of synthetic β-carboline

Kimberly Brito Tecchio1, Fernanda de Moura Alves2, Janaina Domingas Alves3

  • 1Laboratório de Biologia Celular e Mutagênese (LaBCeM), Universidade Federal de São João del Rei (UFSJ), Campus Centro Oeste, Divinópolis, MG 35501-296, Brazil; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei (UFSJ), Campus Centro Oeste, Divinópolis, MG 35501-296, Brazil.

Mutation Research. Genetic Toxicology and Environmental Mutagenesis
|September 26, 2024

View abstract on PubMed

Summary
This summary is machine-generated.
Keywords:
Anticancer prototypesComet assayMicronucleus assayin silicoβ-carboline alkaloids

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Two novel synthetic beta-carboline alkaloids, NQBio-06 and NQBio-21, show potential as antitumor agents. Both compounds exhibit cytotoxicity and mutagenicity, with NQBio-21 demonstrating genotoxicity, warranting further investigation for cancer therapy.

Area of Science:

  • Medicinal Chemistry
  • Pharmacology
  • Toxicology

Background:

  • Synthetic beta-carboline alkaloids are explored as potential antitumor agents.
  • Understanding their cytotoxic, genotoxic, mutagenic, and toxicological profiles is crucial for drug development.

Purpose of the Study:

  • To evaluate the in vitro cytotoxic, genotoxic, and mutagenic potential of NQBio-06 and NQBio-21.
  • To determine the in silico ADME parameters and in vivo acute toxicity of these compounds.
  • To assess their potential as anticancer chemotherapeutic agents.

Main Methods:

  • In vitro cytotoxicity assessed using MTT assay.
  • Genotoxicity evaluated via Comet assay and mutagenicity via Micronucleus assay.
  • In silico ADME properties predicted using computational models; acute toxicity assessed in mice.

Main Results:

  • NQBio-06 showed higher cytotoxicity against ovarian cancer cells (IC50 = 2.5 µM), NQBio-21 against breast cancer cells (IC50 = 6.9 µM).
  • NQBio-21 was genotoxic, and both compounds were mutagenic, with effects enhanced by metabolic activation (S9 fraction).
  • In silico analysis indicated good drug-likeness and absorption; in vivo studies revealed low acute toxicity.

Conclusions:

  • NQBio-06 and NQBio-21 exhibit promising anticancer potential through mechanisms involving DNA damage.
  • Metabolic activation enhances the genotoxic and mutagenic effects of these beta-carboline alkaloids.
  • Further research into these compounds could lead to novel chemotherapeutic agents.