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A Regioselective Synthesis of Carbazole‐Appended Dispiropyrrolothiazoles/Pyrrolidines: Synthesis, Computational Studies and In Vitro Anticancer Activity
Author(s) -
Arya Kripalaya Ratheesh,
Sparkes Hazel A.,
Pandiyan Baskaran Vijaya,
Rajendra Prasad Karnam Jayarampillai
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201801331
Subject(s) - regioselectivity , carbazole , chemistry , cycloaddition , acridine orange , acridine , density functional theory , ethidium bromide , dapi , stereochemistry , combinatorial chemistry , photochemistry , computational chemistry , organic chemistry , apoptosis , dna , biochemistry , catalysis
Anti‐oncological active carbazole appended dispiroindenoquinoxalinepyrrolothiazoles and dispiroacenaphthylenepyrrolidines were synthesized regioselectively via 1,3‐dipolar cycloaddition reaction of azomethine ylide to exocyclic linkage of dipolarophile. The synthesized spiranic compounds are fully characterized by means of spectral, X‐ray crystallography and elemental analysis. Computational details of theoretical calculations have been discussed for compound 4 g ( p ‐Cl‐phenyl substituted pyrrolothiazole‐carbazole system) using DFT (Density Functional Theory) approach at the M06‐2X/LANL2DZ level of theory. The cytotoxic effects of the dispiro compounds were examined on cancerous cell lines such as lung cancer (A549) and breast cancer (MCF‐7) cell lines. Compound 4 g was found to be the most promising derivative against A549 (20±1.0 μg/ml) and MCF‐7 (21±1.5 μg/ml) cells. Furthermore, the morphological changes and apoptotic induction of the promising candidates have been studied by AO/EB (Acridine Orange/Ethidium Bromide) and DAPI (4′,6‐diamidino‐2‐phenylindole) staining methods.