Highly functionalized tetrahydropyridines are cytotoxic and selective inhibitors of human puromycin sensitive aminopeptidase

Eur J Med Chem. 2015 Dec 1:106:26-33. doi: 10.1016/j.ejmech.2015.10.026.

Raghunath Aeluri ¹, Roopa Jones Ganji ², Anil Kumar Marapaka ², Vijaykumar Pillalamarri ², Manjula Alla ³, Anthony Addlagatta ⁴

Affiliations

1 Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500607, India.
2 Center for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500607, India.
3 Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500607, India. Electronic address: manjula@iict.res.in.
4 Center for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500607, India. Electronic address: anthony@iict.res.in.

PMID: 26513642 DOI: 10.1016/j.ejmech.2015.10.026

Abstract

Efficient one-pot five-component synthetic protocols for highly functionalized tetrahydropyridines (THPs) and their biological evaluation have been illustrated. Synthesis of novel functionalized tetrahydropyridines containing differential substitutions at 2,6-positions has been achieved via a modified MCR. Cytotoxic studies of 23 synthesized compounds have been carried out against three different cell lines, namely A-549, HeLa and HepG2, wherein some compounds have displayed appreciable cytotoxicity. Further, investigation of Enzyme inhibition by the synthesized THPs has been carried out against four members of M1 family aminopeptidases. Several compounds have selectively inhibited only one member of this Enzyme family i.e., human puromycin sensitive Aminopeptidase (hPSA). Among the compounds; 4b, 9b, 9e and 10a demonstrated best inhibition against hPSA.

Keywords

Cytotoxicity; Multicomponent reaction; Puromycin sensitive aminopeptidase and inhibitors; Tetrahydropyridine.

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