Novel Aryl Substituted sulfonyl piperazine derivatives:  Tandem one-pot multi component synthesis via palladium catalyzed Suzuki-Miyaura cross coupling, structure studies and evaluation of anticancer activity

Novel N,N -substituted biphenyl sulfonyl piparazines were synthesized through a tandem one-pot reaction of N- substituted piparazines with p -bromosulfonyl chloride in DCM, followed by the palladium catalyzed cross coupling with aryl boronic acids at room temperature and atmospheric pressure. The N - p -bromosulfonylpiparazine intermediate was isolated and crystals obtained through slow evaporation technique was subjected to single crystal diffraction studies to get the structural insights. The study revealed the crystallization in triclinic lattice with P1 space group with each asymmetric unit comprising of two molecules A & B in a nonplanar geometry. The piperazine ring in each molecule was seen to have a puckering environment with Chair conformation. Hirshfeld surfaces mapped on d _norm property and two-dimensional fingerprint graphs provided the types and extent of contribution of intermolecular interaction present in the crystal. The relevant two-dimensional fingerprint graphs revealed H…H, H…C, H…O, and H…Br to be the main forces leading to the crystallization of the intermediate. The novel biphenyl N -sulfonyl piperazine compounds obtained by the Suzuki-Miyaura cross coupling reaction were isolated, characterized and subjected to insilico and invitro anticancer investigations. Biological activity prediction and in-silico ADMET analysis performed using Swiss ADME and ProTox-II tools gave an insight into the pharmacokinetic properties and safety profiles of the synthesized molecules. Synthesized compounds were predicted to have high gastrointestinal absorption and termed safe for organ toxicity parameters. Also, molecular docking studies were conducted using Autodock Vina and Discovery Studio to predict and analyse the binding affinity and interaction of the novel piperazine molecules with survivin protein and human B-DNA. Compound 5a showed highest binding affinity of -8.2 kcal/mol with survivin. Docking of compounds 5 with DNA showed binding affinity of -9.6 kcal/mol. In addition, the cytotoxic effect of the molecules on U87 (glioblastoma) and OVCAR3 (ovarian carcinoma) cell lines, by MTT assay demonstrated appreciable results, suggesting them as prospective candidates for anticancer agents.