Synthesis and biological evaluation of phthalimide dithiocarbamate and dithioate derivatives as anti-proliferative and anti-angiogenic agents-I

Abstract

A facile synthesis of new phthalimide dithiocarbamate and dithioate analogs 8a-j, 9a-e and 9g-j were achieved by the reaction of N-chloromethyl and N-bromoethylphthalimide with carbon disulfide (CS2) and various amines. The structures of the synthesized analogs were elucidated by spectroscopic methods, including IR, 1 H NMR and 13 C NMR, and ESI-HRMS techniques. The antiproliferative activity of the newly synthesized compounds was also evaluated against various human cancer cell lines. The compound 9e and 9i exhibited the highest activity against human breast adenocarcinoma MCF-7 and hepatocellular carcinoma HepG2 cells. Compound 8f showed better antiproliferative effect against colon carcinoma HCT-116 and cervical carcinoma HeLa compared to thalidomide. The binding affinity to vascular endothelial growth factor receptor (VEGFR) of some compounds was assessed in addition to molecular docking study. Compounds 9e and 9i showed high docking score values and they significantly declined the concentration of VEGFR. KEYWORDS

Synthesis and study of N, N` -(ethane-1,2-diyl)bis(1-phenyl methanimine) and thier complex derivative with in-vivo and in-vitro Bacteryal biological study

“…are organosulphur compounds. Their metal complexes have highly attracted in research attention due to some reasons such as: Its diverse uses and its fascinating biological, structural, magnetic, electrochemical and thermal properties [1][2][3][4][5][6][7]. Dithiocarbamates can be used to serve many functions, for example, they are used as accelerators in vulcanization, they are used as high-pressure lubricants, they are also used as fungicides, pesticides [2] and medicinal chemistry [3].…”

“…Dithiocarbamates can be used to serve many functions, for example, they are used as accelerators in vulcanization, they are used as high-pressure lubricants, they are also used as fungicides, pesticides [2] and medicinal chemistry [3]. Furthermore, Dithiocarbamate species are considered potential drug candidates that have been shown to be anticancer [4] anti-bacterial and antifungal activities [5] with good examples of resistance in industry. For instance, the formation of Zn-dithiocarbamate complexes showed resistance for increasing temperature and conductivity.…”

Design, Synthesis and Biological Evaluation of Novel Indole-Thalidomide Hybrids Analogs

“…Therefore, the research for new cancer-treating agents is an important area in both organic and medicinal chemistry. Indoles are the main components of many drugs and some biologically active compounds, and the development of new forming methods leading to indole derivatives has attracted much attention in organic synthesis Recently, our group synthesizes novel indole, phthalimide, thalidomide analogs and studies intensively their antitumor activity [36][37][38][39][40][41][42][43][44][45]. Based on the previously mentioned facts, the current study aimed to synthesize novel Thalidomide-Indole hybrids by Knoevenagel condensation between 1Hindole-3-carbaldehyde and different active methylene Compounds.…”

Novel phthalimide based analogues: design, synthesis, biological evaluation, and molecular docking studies

“…Bearing in mind our program in the synthesis of biologically active heterocyclic compounds 27–32 and the molecular pharmacophores ( I - V ) outlined in Figure 1 and their structural requirements 33–36 , some phthalimide derivatives were designed after exploring molecular hybridization approaches with pyrazole, imidazo[1,2- b ]-pyrazole, pyrazolopyrimidine, pyrazolo-triazine moieties (Figure 1). All the newly prepared phthalimide derivatives were subjected for evaluation of both antimicrobial and anticancer activities with the study of their Drug-Likeness and Toxicity parameters.…”