Synthesis of new class of spirocarbocycle derivatives by multicomponent domino reaction and their evaluation for antimicrobial, anticancer activity and molecular docking studies

• Published in: European journal of medicinal chemistry 2014-08, Vol.83, p.190-207
• Main Authors: Sudhapriya, N., Perumal, P.T., Balachandran, C., Ignacimuthu, S., Sangeetha, M., Doble, Mukesh
• Format: Article
• Language: English
• Subjects: Anti-Infective Agents - chemical synthesis; Anti-Infective Agents - chemistry; Anti-Infective Agents - metabolism; Anti-Infective Agents - pharmacology; Anticancer activity; Antimicrobial activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Bacteria - drug effects; Cell Line, Tumor; Chemistry Techniques, Synthetic; DNA Gyrase - chemistry; DNA Gyrase - metabolism; Humans; Molecular docking; Molecular Docking Simulation; Multicomponent reaction; Protein Conformation; Receptor Protein-Tyrosine Kinases - chemistry; Receptor Protein-Tyrosine Kinases - metabolism; Spiro Compounds - chemical synthesis; Spiro Compounds - chemistry; Spiro Compounds - metabolism; Spiro Compounds - pharmacology; Spirocarbocycle; Vinylogous Michael addition
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2014.05.065

A series of 25 new spirocarbocycles were synthesized by a three component reaction that involves few cyclic nucleophiles, vinyl malononitriles and aldehydes with variable substitution patterns. All the synthesized compounds were evaluated for their antimicrobial activity and the compounds showed significant activity. Synthesized compounds 4c, 4i and 6i showed good anticancer activity against A549 cancer cell line. Molecular docking studies indicated that compound 4i had the greatest affinity for DNA gyrase receptor than others and compound 6i had the greatest affinity for anaplastic lymphoma kinase (ALK) receptor. These compounds can be better therapeutic agents for microbial and cancer cell lines. Synthesis of spirocarbocycles was achieved by a three component reaction of cyclic nucleophiles, vinyl malononitriles and aldehydes with variable substitution patterns. [Display omitted] •One pot synthesis of spirocarbocycles was developed using l-proline.•Ordinary reaction conditions, wide substrate scope, excellent yield (72–90%).•Most of the compounds exhibited moderate to good activity against bacteria.•Docking study of ligands with receptor was further supported by in vitro results.•Compound 6i showed very good affinity towards the ALK receptor.