A facile stereoselective synthesis of dispiro-indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids and evaluation of their antimycobacterial, anticancer and AchE inhibitory activities

Bharkavi C 1 , Vivek Kumar S 1 , Ashraf Ali M 2 , Osman H 3 , Muthusubramanian S 4 , Perumal S 5

Affiliations 

  • 1 Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai, Tamil Nadu 625 021, 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, Tamil Nadu 625 021, India. Electronic address: muthumanian2001@yahoo.com
  • 5 Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai, Tamil Nadu 625 021, India. Electronic address: subbu.perum@gmail.com
Bioorg Med Chem, 2016 11 15;24(22):5873-5883.
PMID: 27687968 DOI: 10.1016/j.bmc.2016.09.044

Abstract

A facile stereoselective synthesis of novel dispiro indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids has been achieved by 1,3-dipolar cycloaddition of azomethine ylides, generated in situ from ninhydrin and sarcosine/thiaproline, on a series of 3-benzylidenethiochroman-4-ones. The synthesised compounds were screened for their antimycobacterial, anticancer and AchE inhibition activities. Compound 4l (IC50 1.07μM) has been found to exhibit the most potent antimycobacterial activity compared to cycloserine (12 times), pyrimethamine (37 times) and ethambutol (IC50 <1.56μM) and 6l (IC50=2.87μM) is more active than both cycloserine (4 times) and pyrimethamine (12 times). Three compounds, 4a, 6b and 6i, display good anticancer activity against CCRF-CEM cell lines. Compounds 6g and 4g display maximum AchE inhibitory activity with IC50 values of 1.10 and 1.16μmol/L respectively.

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