Ultrasound Promoted Green Synthesis, Docking Study of Indole Spliced Thiadiazole, α-amino Phosphonates as Anticancer Agents and Antityrosinase Agents

Author(s): Annapratima G. Nikalje*, Pramod A. Gawhane, Shailee V. Tiwari, Jaiprakash N. Sangshetti, Manoj G. Damale.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 18 , Issue 9 , 2018

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Regardless of recent advances in the development of clinically authorized anticancer agents the number of deaths due to cancer is increasing day by day all over the world. The aim of this research work is to synthesis novel anticancer agents.

Method: In this work, a new series of diethyl ((1H-indole-3-yl)((5-phenyl-1,3,4-thiadiazole-2-yl)amino) methyl)phosphonate derivatives 6(a-j) were designed and synthesized in Ultrasound by green protocol using Kabachnik-Fields reaction. The structures of the synthesized compounds were confirmed by spectral analysis such as elemental analyses, IR, 1H NMR, 13C NMR, 31P NMR and mass spectra. The synthesized compounds 6(a-j) were appraised for their in vitro anticancer activity against human cancer cell lines such as SK-MEL-2 (melanoma), IMR-32 (Neuroblastoma), HT-29(Colon) and also on normal murine embryonic fibroblast NIH/3T3 by Sulforhodamine B (SRB) assay, using Adriamycin as a standard drug.

Result: The treatment of SK-MEL-2 cancer cells with 6i showed apoptosis and morphological changes like cell shrinkage, cell wall deformation and reduced number of viable cells. The synthesized derivatives were also evaluated for their anti-tyrosinase effect. Nearly all the tested derivatives have been found to be potent tyrosinase inhibitors.

Conclusion: Nearly all the compounds were tested, the docking study was performed and indicates that the compounds have good binding interactions with tyrosine kinase enzyme. Absorption, Distribution, Metabolism and Elimination (ADME) properties of the synthesized compounds were also analyzed which manifested their potentiality to thrive as good oral drug candidates.

Keywords: Indole, thiadiazole, Kabachnik-Fields reaction, in-vitro anticancer activity, docking, ADME prediction.

Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 18
ISSUE: 9
Year: 2018
Page: [1267 - 1280]
Pages: 14
DOI: 10.2174/1871520618666180417163226
Price: $58

Article Metrics

PDF: 13
HTML: 1