Pharmacologically active compounds in the environment and their chirality

Abstract

Pharmacologically active compounds including both legally used pharmaceuticals and illicit drugs are potent environmental contaminants. Extensive research has been undertaken over the recent years to understand their environmental fate and toxicity. The one very important phenomenon that has been overlooked by environmental researchers studying the fate of pharmacologically active compounds in the environment is their chirality. Chiral drugs can exist in the form of enantiomers, which have similar physicochemical properties but differ in their biological properties such as distribution, metabolism and excretion, as these processes (due to stereospecific interactions of enantiomers with biological systems) usually favour one enantiomer over the other. Additionally, due to different pharmacological activity, enantiomers of chiral drugs can differ in toxicity. Furthermore, degradation of chiral drugs during wastewater treatment and in the environment can be stereoselective and can lead to chiral products of varied toxicity. The distribution of different enantiomers of the same chiral drug in the aquatic environment and biota can also be stereoselective. Biological processes can lead to stereoselective enrichment or depletion of the enantiomeric composition of chiral drugs. As a result the very same drug might reveal different activity and toxicity and this will depend on its origin and exposure to several factors governing its fate in the environment. In this critical review a discussion of the importance of chirality of pharmacologically active compounds in the environmental context is undertaken and suggestions for directions in further research are made. Several groups of chiral drugs of major environmental relevance are discussed and their pharmacological action and disposition in the body is also outlined as it is a key factor in developing a full understanding of their environmental occurrence, fate and toxicity. This review will be of interest to environmental scientists, especially those interested in issues associated with environmental contamination with pharmacologically active compounds and chiral pollutants. As the review will outline current state of knowledge on chiral drugs, it will be of value to anyone interested in the phenomenon of chirality, chiral drugs, their stereoselective disposition in the body and environmental fate (212 references).

Chiral pollutants and their significance in the environment

“…Çevresel ortamlar, endüstriyel veya evsel nitelikteki atıksuların su, toprak ve sedimana ulaştırdığı kiral kirleticiler ile sürekli kirlenmektedir [1]. En önemli noktasal kaynaklarından birisi de insanlar tarafından kullanılan ilaçların bozunmayan kısımlarının evsel/hastane atıksuları veya üretildikleri endüstrilerin atıksularıyla çevresel ortamlara ulaşmalarıdır [17], [18].…”

“…Çevre kirliliği araştırmalarında çoğunlukla fenoksi alkanoik asit herbisitler, asetamid pestisitler, organofosforlu bileşikler, piretroidler, farmasötikler gibi maddeler araştırmalara konu olmuştur [18]. Bunun yanı sıra KOK sınıfında yer alan kimyasallar da kiral özellikte bileşikler içermektedir.…”

“…Bu ilaçların insanlar tarafından kullanılması sonucu evsel/hastane atıksuları veya üretildikleri endüstrilerin atıksularıyla çevreye yayılırlar [18].…”

(−)-UB006: A new fatty acid synthase inhibitor and cytotoxic agent without anorexic side effects

“…It is well-known that the stereochemistry of a drug could determine its biological activity [11,12]. The preparation of (-)-C75 and (+)-C75 enantiomers separately was not reported until recently [13].…”

Catálise assimétrica no Brasil: desenvolvimento e potencialidades para o avanço da indústria química brasileira

“…Em muitos casos, a atividade farmacológica está restrita a um dos enantiômeros enquanto que o outro pode ser responsável por reações adversas e/ou contaminação ambiental. 3 Devido à atividade farmacológica distinta, os enantiômeros de fármacos quirais podem ainda diferir em sua toxicidade. Da mesma forma, a distribuição dos diferentes enantiômeros do mesmo fármaco quiral no ambiente aquático e biota também pode ser estereosseletiva, e com isso a sua degradação durante o tratamento de águas residuais e no ambiente pode ocorrer de maneira estereosseletiva e conduzir a produtos quirais de toxicidades variadas, podendo levar a uma contaminação significativa do meio ambiente.…”