title: Synthesis and evaluation of novel amonafide-polyamine conjugates as anticancer agents.
abstract: With the aim of upregulating antitumor efficacy and downregulating adverse effects, the amino group in the three-position of amonafide aromatic ring was modified by coupling with different amine/polyamine motifs via two linkers. Two series of naphthalimide derivatives were designed and synthesized and evaluated for their antitumor properties in vitro and in vivo. The preliminary in vitro trials revealed that compounds with urea as the linker were not active, and the presence of aspirin elevated the potency of 6k against tumor cells, wound healing, and the protein expression of cyclic D1 and MMP9. The in vivo trials on three H22 tumor transplant models demonstrated that the combination of 6k and aspirin markedly improved the efficacy in terms of inhibitive effect, pulmonary metastasis, and extension of the life span. More importantly, the combination of 6k and aspirin displayed the reduced side-effects compared to that of amonafide.
authors.affiliation: College of Chemistry and Chemical Engineering, Henan University, Kaifeng, China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Pharmaceutical College, Henan University, Kaifeng, China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Pharmaceutical College, Henan University, Kaifeng, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Pharmaceutical College, Henan University, Kaifeng, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Pharmaceutical College, Henan University, Kaifeng, China.
authors.forename: Songqiang
authors.initials: S
authors.lastname: Xie
authors.affiliation: Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng, China.
authors.forename: Chaojie
authors.initials: C
authors.lastname: Wang
mesh_terms: D000225:Adenine; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D008297:Male; D008856:Microscopy, Fluorescence; D053644:Naphthalimides / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D063065:Organophosphonates; D011073:Polyamines / Q000737:chemistry*; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D053644:Naphthalimides; D063065:Organophosphonates; D011073:Polyamines; C037020:amonafide; D000225:Adenine
keywords: amonafide; antitumor; naphthalimide; polyamine; synthesis