Synthesis, Biological Evaluation, Docking and QSAR Studies of Some Novel Naphthalimide Dithiocarbamate Analogs as Antitumor and Anti- Inflammatory Agents

Maram H Zahra,Hussein Agwa,Amany M A Osman

doi:10.4172/2161-0444.1000417

Abstract

A series of novel naphthalimide dithiocarbamate 4a-f, 5a-f were efficiently synthesized via introduce dithiocarbamate and dithioate side chain onto the naphthalic anhydride core. The structures of the synthesized analogs were elucidated by spectroscopic methods, including IR,1H and 13C NMR, and (ESIHRMS) techniques. The anti-cancer activities of the generated naphthalimide derivatives 4c, 4d, 4e, 4f, and 5d were evaluated against 21 tumour cell lines; inculding 10 tumor subpanels using MTT assay. Analogue 4c offer antitumor activity with an IC50 of 10.54 μM against SKBR3 breast cancer cells. Compound 4d showed varying degrees of antitumor activities towards several tumour cell lines ranging from 21.1 to 71.7 μM. In addition to the antitumor activities; the synthesized compounds were evaluated for their In vitro anti-inflammatory activity. Compounds 4c and 4d revealed potent anti-inflammatory properties in comparison with the reference drug celecoxib. Molecular docking studies provided complementary theoretical support for experimental biological data.

Highlights

The development of new classes of chemotherapeutic agents to treat cancer patients remains an important goal of the medical community worldwide
Among the agents directly intercalating with DNA; naphthalimides which belong to the cyclic imides class represent an important moiety in the antitumor drug design concept [6]
Naphthalimide [1H-benz [de] isoquinoline-1, 3-(2H)-diones] is considered as one of the simplest poly cyclic amides from a famous class of intercalating agents consisting of a flat, generally π –deficient aromatic or heteroaromatic system which bind to DNA by insertion between base pairs of the double helix [12,13,14]

Summary

Introduction

The development of new classes of chemotherapeutic agents to treat cancer patients remains an important goal of the medical community worldwide. Our group recently reported the synthesis of a novel thalidomide-containing dithiocarbamate moiety; several derivatives exhibited potent anti-cancer activity [27,28]. 2-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)ethyl hexadecylcarbamo-dithioate (4c): White solid; mp 138–140°C, Yield 76%. 13C NMR (DMSO-d6) δ 33.95 (NCH2CH2S), 38.47 (NCH2CH2S), 52.38

Results

Conclusion