No contexto das nitrosaminas, compreender a relação entre a estrutura química e o potencial carcinogênico possui relevância significativa.
Recentemente, com a divulgação da abordagem CPCA (Carcinogenic Potency
Categorisation Approach, EMA/409815/2020), tornou-se mais evidente que características estruturais podem diretamente aumentar ou diminuir o mecanismo de ativação metabólica (α-hidroxilação) e, espera-se, que tenham um efeito correspondente na potência carcinogênica.
Ou seja, é possível gerar uma previsão do potencial mutagênico e da potência carcinogênica de uma N-nitrosamina com base em suas características estruturais, certo?
Bom, a partir do artigo Strategies for Assessing Acceptable Intakes for Novel N-Nitrosamines Derived from Active Pharmaceutical Ingredients adaptei um resumo para auxiliar você em seus estudos sobre nitrosaminas.
USP_Infográfico nitrosaminas.pdf (77.5 KB)
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Wonderful @lucas10mauriz as usual Appreciate your selfless contribution to our community!!
Just wanted to add on few thoughts which i perceive in current context:
The CPCA approach with more reliance on chemical structural orientation and past knowledge base on few structural features have really helped currently to come out of this nitrosamines guilt. No doubt!! However, i foresee pure reliance on chemistry features with less established database might not serve the complete purpose down the line. Parallel understanding of human biology and physiology with these structures might need to go hand in hand. That comes with few biological experimentations (Not unnecessary animal testing i mean!)
I felt carbonyls have mixed data some supporting potent carcinogenicity and some supporting weak carcinogenicity. May be other experts @David etc. can add more clarity.
Pertinently, NDSRI’s like complex structures might need some careful evaluation because it may not be simple nitroso or surrounding alpha carbons that needs addressable, but the variety of features collectively decide their fate in human biology. Despite of above fact, it is also worthy to note our human biology do also have adaptive and repair pathways to handle complex hazardous chemistry!
@Pradpharma , thank you for your words.
You sure! the potential problem with relying only on chemistry features, especially with databases lacking strong validation, highlights an important concern. Chemical interactions are complex, and their various effects require a thorough understanding beyond just the structure. While chemistry provides valuable insights into molecules, their properties, and how they react, it’s crucial to also understand how they interact within living organisms to fully grasp their wider implications.
However, I have no doubts that the CPCA is a significant advancement and a game-changer in this matter. May we continue to improve ourselves further, Do you agree?
I agree with your thoughts!