Dapson in heterocyclic chemistry, part VIII: synthesis, molecular docking and anticancer activity of some novel sulfonylbiscompounds carrying biologically active 1,3-dihydropyridine, chromene and chromenopyridine moieties

Abstract

Several new sulfonebiscompounds having a biologically active 1,2-dihydropyridine-2-one 3-19, acrylamide 20, chromene 21, 22 and chromenopyridine 23, 24 moieties were synthesized and evaluated as potential anticancer agents. The structures of the products were confirmed via elemental analyses and spectral data. The screening tests showed that many of the biscompounds obtained exhibited good anticancer activity against human breast cell line (MCF7) comparable to doxorubicin which was used as reference drug. Compounds 11, 17 and 24 showed IC50 values 35.40 μM, 29.86 μM and 30.99 μM, respectively. In order to elucidate the mechanism of action of the synthesized compounds as anticancer agents, docking on the active site of farnesyltransferase and arginine methyltransferase was also performed and good results were obtained.

Scheme 1

Synthetic pathways used to obtain compounds 2-16.

Scheme 2

Synthetic pathways used to obtain compounds 17-20.

Scheme 3

Synthetic pathways used to obtain compounds 21-24.

Figure 1

Co-crystallized sulfone ligand on the active site of farnesyltransferase.

Figure 2

Compound 24 on the active site of farnesyltransferase.

Figure 3

Co-crystallized S-adenosyl methionine ligand on the active site of arginine methyltransferase (PRMT1).

Figure 4

Compound 24 on the active site of arginine methyltransferase (PRMT1).