SYNTHESIS AND ANTIPROLIFERATIVE ACTIVITY OF ACRIDINE-SULFONAMIDE CONJUGATES

Feby Awad-Allah Ibrahim and Ibrahim El Tantawy El Sayed*

ABSTRACT

The present study describes the synthesis and antiproliferative evaluation of several acridine analogues carrying sulfonamide and thiouredoside chain at C-9 position. The key intermediate aminoacridines5 were prepared by nucleophilic aromatic substitution (SNAr) of 9-chloroacridine 4 with 4,4'-diaminodiphenylmethane or p-phenylenediamine. The 9-amino derivatives 5 were further reacted with phenylisothiocyanate or arylsulfonlychloridesto afford the corresponding thiourea-, or acridine sulfonamide analogues6 and 7 respectively. Some of the prepared derivatives showed a strong antiproliferative activity against the breast, colon and hepatocellular carcinoma cell lines. Among them, compounds 5b and 8bwere the most potentwith IC50 values 5.88, 8.30, 8.93 and 8.83, 14.51, 9.39 against breast, hepatocellular and coloncarcinoma cell lines respectively.

Keywords: 9-Chloroacridin, Sulfonamide, Synthesis, Antiproliferative Activity.