Title:Ultrasound Promoted Green Synthesis, Docking Study of Indole Spliced Thiadiazole, α-amino Phosphonates as Anticancer Agents and Antityrosinase Agents
VOLUME: 18 ISSUE: 9
Author(s):Annapratima G. Nikalje*, Pramod A. Gawhane, Shailee V. Tiwari, Jaiprakash N. Sangshetti and Manoj G. Damale
Affiliation:Department of Pharmaceutical Chemistry, Y. B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad 431001, M.S, Department of Pharmaceutical Chemistry, Y. B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad 431001, M.S, Department of Pharmaceutical Chemistry, Durgamata Institute of Pharmacy, Dharmapuri, Parbhani, 431401, M.S, Department of Pharmaceutical Chemistry, Y. B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad 431001, M.S, Department of Pharmaceutical Chemistry, Shreeyash Institute of Pharmaceutical Education and Research, Aurangabad 431003, M.S
Keywords:Indole, thiadiazole, Kabachnik-Fields reaction, in-vitro anticancer activity, docking, ADME prediction.
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.
