Design, synthesis, and evaluation of new anti-inflammatory natural products amide derivatives endowed with anti-blood cancer activity towards development of potential multifunctional agents against hematological cancers

New amide derivatives of the natural product 5,6,7-trimethoxyflavanone were designed as multifunctional antiproliferative molecules against blood cancer and the associated inflammatory conditions. The targeted compounds were synthesized efficiently in three linear steps employing known chalcone starting materials. Compounds 2h, 2i, 2l, 2t, 2v and 2x having bromo or nitro substituted-phenyl rings elicited potential inhibitory effects on macrophages production of nitric oxide, PGE2 and TNF-& alpha; which are proinflammatory mediators involved in tumorigenesis and progression of blood cancer. Additionally, evaluation of direct inhibitory effects on the growth of diverse blood cancers including leukemia, lymphoma, and myeloma cell lines unveiled compound 2v as the most potential molecules eliciting at least five-folds the potency of the standard imatinib drug over the used diverse blood cancers. Furthermore, compound 2v showed good selectivity to blood cancer cells rather than normal MRC5 cells. Moreover, compound 2v triggered death of HL60 leukemia cells via apoptosis induction. In conclusion, the natural product-derived compound 2v might serve as a multifunctional lead compound for further development of agents for treatment of blood cancers.

Automated summary

New amide derivatives of the natural product 5,6,7-trimethoxyflavanone were designed and synthesized for their potential antiproliferative effects against blood cancer and inflammation. Compound 2v showed the most promising inhibitory effects on the production of proinflammatory mediators and exhibited significantly higher potency against diverse blood cancers compared to the standard drug imatinib. Moreover, compound 2v showed selectivity towards blood cancer cells and induced apoptosis in HL60 leukemia cells.