One-pot microwave assisted stereoselective synthesis of novel dihydro-2'H-spiro[indene-2,1'-pyrrolo-[3,4-c]pyrrole]-tetraones and evaluation of their antimycobacterial activity and inhibition of AChE

Chelliah Bharkavi; Sundaravel Vivek Kumar; Mohamed Ashraf Ali; Hasnah Osman; Shanmugam Muthusubramanian; Subbu Perumal

doi:10.1016/j.bmcl.2017.05.050

One-pot microwave assisted stereoselective synthesis of novel dihydro-2'H-spiro[indene-2,1'-pyrrolo-[3,4-c]pyrrole]-tetraones and evaluation of their antimycobacterial activity and inhibition of AChE

Bioorg Med Chem Lett. 2017 Jul 15;27(14):3071-3075. doi: 10.1016/j.bmcl.2017.05.050. Epub 2017 May 17.

Authors

Chelliah Bharkavi¹, Sundaravel Vivek Kumar¹, Mohamed Ashraf Ali², Hasnah Osman³, Shanmugam Muthusubramanian⁴, Subbu Perumal⁵

Affiliations

¹ Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625021, Tamil Nadu, India.
² School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia; New Drug Discovery Research, Department of Medicinal Chemistry, Sunrise University, Alwar, Rajasthan 301030, India.
³ School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
⁴ Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625021, Tamil Nadu, India. Electronic address: muthumanian2001@yahoo.com.
⁵ Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625021, Tamil Nadu, India. Electronic address: subbu.perum@gmail.com.

PMID: 28552337
DOI: 10.1016/j.bmcl.2017.05.050

Abstract

An efficient one-pot microwave assisted stereoselective synthesis of novel dihydro-2'H-spiro[indene-2,1'-pyrrolo[3,4-c]pyrrole]-tetraone derivatives through three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ from ninhydrin and sarcosine with a series of 1-aryl-1H-pyrrole-2,5-diones is described. The synthesised compounds were screened for their antimycobacterial and AChE inhibition activities. Compound 4b (IC₅₀ 1.30µM) has been found to display twelve fold antimycobacterial activity compared to cycloserine and it is thirty seven times more active than pyrimethamine. Compound 4h displays maximum AchE inhibitory activity with IC₅₀ value of 0.78±0.01µmol/L.

Keywords: 1,3-Dipolar cycloaddition; AChE inhibition; Azomethine ylides; Diazabicyclic compounds; M. tuberculosis H(37)Rv.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcholinesterase / chemistry
Acetylcholinesterase / metabolism*
Antitubercular Agents / chemical synthesis*
Antitubercular Agents / chemistry
Antitubercular Agents / pharmacology
Cholinesterase Inhibitors / chemical synthesis
Cholinesterase Inhibitors / chemistry
Cholinesterase Inhibitors / pharmacology
Crystallography, X-Ray
Drug Design
Enzyme Activation / drug effects
Inhibitory Concentration 50
Microbial Sensitivity Tests
Microwaves*
Molecular Conformation
Mycobacterium tuberculosis / drug effects
Pyrroles / chemical synthesis
Pyrroles / chemistry*
Pyrroles / pharmacology
Stereoisomerism
Structure-Activity Relationship

Substances

Antitubercular Agents
Cholinesterase Inhibitors
Pyrroles
Acetylcholinesterase