Prediction of pharmacokinetics profile of new cytotoxic compounds from trunk bark and root bark of Citrus x paradisi (Rutaceae)

Abstract

Introduction: According to the WHO, cancer is the second leading cause of death worldwide. In fact, the International Agency for Research on Cancer has estimated that there will be 20 million and 9.7 million new cases of cancer and deaths in 2022, respectively. Although chemotherapy is effective, the drugs used not only attack cancer cells, but also healthy cells. It is in this context that this study is being conducted with the aim to search new drug candidates with fewer side effects.

Material and method: 24 Pharmacokinetic and toxicity parameters of these molecules have been predicted using chemical computational methods.

Results: According to the Lipinski rules, the 1-Formyl-5-Hydroxy-N-Methylindolin-1-ium is the best drug candidate for all pharmaceutical forms and a good lead compound. For oral form, the 23 (s) -isolimonexin and the decyloxycleomiscosin D are not good drugs candidates. However, due to their hydrophilic character, the IV formulations would be appropriate. The 23 (s) -isolimonexin is also a good leader. All those molecules would be highly toxic with a low therapeutic index and eliminated from kidney as metabolites with a short half-life time.

Conclusion: Only 1-Formyl-5-Hydroxy-N-Methylindolin-1-ium would be a good drug candidate and a good lead compound for all pharmaceutical forms. On the other hand, 23(s)-isolimonexine and decyloxycleomiscosin D would not be good drug candidates for oral forms.