Domino Multicomponent Approach for the Synthesis of Functionalized Spiro-Indeno[1,2- b]quinoxaline Heterocyclic Hybrids and Their Antimicrobial Activity, Synergistic Effect and Molecular Docking Simulation

Abdulrahman I Almansour; Natarajan Arumugam; Raju Suresh Kumar; Dhaifallah M Al-Thamili; Govindasami Periyasami; Karuppiah Ponmurugan; Naif Abdullah Al-Dhabi; Karthikeyan Perumal; Dhanaraj Premnath

doi:10.3390/molecules24101962

Domino Multicomponent Approach for the Synthesis of Functionalized Spiro-Indeno[1,2- b]quinoxaline Heterocyclic Hybrids and Their Antimicrobial Activity, Synergistic Effect and Molecular Docking Simulation

Molecules. 2019 May 22;24(10):1962. doi: 10.3390/molecules24101962.

Authors

Abdulrahman I Almansour¹, Natarajan Arumugam², Raju Suresh Kumar³, Dhaifallah M Al-Thamili⁴, Govindasami Periyasami⁵, Karuppiah Ponmurugan⁶, Naif Abdullah Al-Dhabi⁷, Karthikeyan Perumal⁸, Dhanaraj Premnath⁹

Affiliations

¹ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. almansor@ksu.edu.sa.
² Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. anatarajan@ksu.edu.sa.
³ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. sraju@ksu.edu.sa.
⁴ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. daife54321@hotmail.com.
⁵ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. pkandhan@ksu.edu.sa.
⁶ Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. pkaruppiah@ksu.edu.sa.
⁷ Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. naldhabi@ksu.edu.sa.
⁸ Department of Chemistry and Biochemistry, The Ohio State University, 151 W. Woodruff Ave, Columbus, OH 43210, USA. pkarthikjaya@gmail.com.
⁹ Department of Bioscience and Technology, Karunya Institute of Technology and Science, Branch of Bioinformatics, School of Agriculture and Biosciences, Karunya Nagar, Coimbatore-641114, India. prems.bioinfo@gmail.com.

Abstract

An expedient synthesis of hitherto unexplored novel hybrid heterocycles comprising dispiropyrrolidine, N-styrylpiperidone and indeno[1,2-b]quinoxaline units has been developed via domino multicomponent 1,3-dipolar cycloaddition strategy employing a new class of azomethine ylide in ionic liquid, 1-butyl-3-methylimidazolium bromide. This domino protocol involves, 1,3-dipolar cycloaddition and concomitant enamine reaction affording the dispiropyrrolidine tethered N-styrylpiperidone hybrid heterocycles in moderate to good yield in a single step. These compounds were evaluated for their antimicrobial activity against bacterial and fungal pathogens, therein compounds 8f, 8h, and 8l displayed significant activity against tested microbial pathogens. The synergistic effect revealed that the combination of compound 8h with streptomycin and vancomycin exhibited potent synergistic activity against E. coli ATCC 25922. In addition, molecular docking simulation has also been studied for the most active compound.

Keywords: antimicrobial activity; dispiropyrrolidine; docking studies; domino multicomponent reaction; indeno[1,2-b]quinoxaline; synergistic effect.

MeSH terms

Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Cycloaddition Reaction
Drug Synergism
Escherichia coli / drug effects
Imidazoles / chemistry
Microbial Sensitivity Tests
Molecular Docking Simulation
Molecular Structure
Quinoxalines / chemical synthesis*
Quinoxalines / chemistry
Quinoxalines / pharmacology*
Streptomycin / pharmacology
Structure-Activity Relationship
Vancomycin / pharmacology

Substances

Anti-Bacterial Agents
Imidazoles
Quinoxalines
1-butyl-3-methylimidazolium chloride
Vancomycin
Streptomycin

Grants and funding

Deanship of Scientific Research at King Saudi University for the Research grant RGP-026./Deanship of Scientific Research, King Saud University