Synthesis and Cytotoxicity Evaluation of Naphthalimide Derived N-Mustards

Abstract

A series of N-mustards, which was conjugated to mono-or bis-naphthalimides with a flexible amine link, were synthesized and evaluated for cytotoxicity against five cancer cell lines (HCT-116, PC-3, U87 MG, Hep G2 and SK-OV-3). Several compounds displayed better activities than the control compound amonafide. Further evaluations by fluorescence spectroscopy studies and DNA-interstrand cross-linking assays revealed that the derivatives showed both alkylating and intercalating properties. Among the derivatives, the bis-naphthalimide N-mustard derivative 11b was found to exhibit the highest cytotoxic activity and DNA cross-linking ability. Both 11b and 7b induce HCT-116 cell apoptosis by S phase arrest.

1,8‐Naphthalimide: A Potent DNA Intercalator and Target for Cancer Therapy

“…Mono‐ 67 and 68 , and bis‐ 69 and 70 (Figure ), conjugates of N‐mustard derivatives of bis‐naphthalimides have also been explored as both alkylating agents and intercalators by Lou and coworkers . These compounds were screened for their cytotoxic activities against five cell lines including HCT‐116, PC‐3, U87MG, Hep G2 and SK‐OV‐3 with amonafide as internal reference.…”

Synthesis and in vitro anticancer evaluation of 1,8-naphthalimide N(4) and S(4)-derivatives combining DNA intercalation and alkylation capabilities

“…Thus, 5 and 6 were developed by connecting the 1,8-naphthalimide unit present in amonafide with the N,N-bis (2-chloroethyl) amino alkylating group present in chlorambucil via the imide nitrogen atom. Reportedly, molecule 5 shows high cytotoxicity against murine carcinoma cell lines [17][18][19]. Recent studies on 3-nitro-1,8-naphthalimide similarly conjugated with nitrogen mustards also showed significant antitumour activity and low systemic toxicity against hepatocellular carcinoma compared to 1 [20] (Fig.…”