Abstract
Objective: The present study was designed to study the anticancer activity of a series of novel analogs of phenothiazine with dithiocarbamate as a side chain. Methods: A novel series of derivatives containing dithiocarbamate as a side chain at the tenth position of phenothiazine nucleus were synthesized, characterized by spectral analysis, and evaluated for their antimitotic and antioxidant activity using germinated Bengal gram seeds and 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, respectively. A quantitative estimate of drug-likeness was also performed, which calculated the molecular properties and screened the molecules based on drug-likeness rules. Further, molecular docking study was performed for finding the binding affinity with tubulin protein to rationalize their anticancer activity. Results: The results revealed that the antioxidant activity of compounds 3e, 3g, 3i, 3j and standard Ascorbic acid were 10 mmol, 14 mmol, 16 mmol, 16 mmol and 35 mmol, respectively. Further compounds 3e, 3g, 3h and 3i have shown promising antimitotic activity. Compound 3i (-9 K. Cal/mol) showed the highest binding energies towards tubulin protein when compared to standard drug colchicine (-8.6 K. Cal/mol). Among all, compound 3i showed promising antimitotic and antioxidant activity, which correlated with insilico docking studies. Conclusion: Dithiocarbamate substituted phenothiazine derivatives proved to be encouraging leads as tubulin inhibitors.
Highlights
In recent years, the design and synthesis of novel bioactive compounds gained significant applications in the pharmaceutical industries
Phenothiazine ring systems are of considerable interest as it is a core structure in various synthetic pharmaceuticals displaying a broad spectrum of biological activities including tranquilizers, antiinflammatory, antimalarial, anti-psychotropic, antimicrobial, antitubercular, antitumor, antihistamine and analgesic properties [13]
The synthesis of title compounds obtained by reaction of dithiocarbamate with N-(2-chloro-acetyl) phenothiazine in the presence of anhydrous Potassium Carbonate (K2CO3) using various amines as shown in
Summary
The design and synthesis of novel bioactive compounds gained significant applications in the pharmaceutical industries. Phenothiazine ring systems are of considerable interest as it is a core structure in various synthetic pharmaceuticals displaying a broad spectrum of biological activities including tranquilizers, antiinflammatory, antimalarial, anti-psychotropic, antimicrobial, antitubercular, antitumor, antihistamine and analgesic properties [13]. Phenothiazine derivatives having an acyl side chain playing a crucial role in anticancer activity. Several literature reports indicate inclusion of dithiocarbamate as a linker or side chain in active pharmacophore improves the overall biological profile [4,5,6,7]. Inspired by these findings, we designed novel dithiocarbamate substituted N-acyl phenothiazine derivatives as anticancer agents
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
