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Applicant:
Indian Institute of Technology (IIT) Gandhinagar 
Title:
PROCESS FOR THE PREPARATION OF N-SUBSTITUTED PHENOTHIAZINE DERIVATIVES 
Inventor(s):
"KIRUBAKARAN SIVAPRIYA; THIRUVENKATAM VIJAY; HUSSAIN JAVEENA; ALTHAF SHAIK; SIDDHANT BHOIR" 
Applicant:
Indian Institute of Technology (IIT) Gandhinagar 
Application type:
Provisional - 2019-12-31 
Application Number:
201921054699 
Applied at:
India 
Entered by:
Indian Institute of Technology (IIT) Gandhinagar 
Abstract:
Tousled like kinase, is a serine/ threonine kinase present in the human body specifically phosphorylated Asf1, H3 and Rad9 protein. The TLKs are involved in DNA repair & replication, transcription, chromatin assembly and chromosome segregation. They are present in two different forms i.e. TLK1 and TLK2 out of which TLK1/1B phosphorylates specifically Asf1 which is responsible for chromatin assembly and activation of Rad9. TLK1B repairs the double strand break (DSB) ends by disassembling the chromatin present nearby to repair proteins. Hence, TLK1/1B facilitates the DDR and DSB repair. The over- expression of TLK1/1B in different cancer cell lines act as a target for therapeutic intervention and to design drug like molecules to inhibit the pathways of phosphorylation to prevent DDR and DSB repair. Thioridazine (THD), one of TLK1/1B inhibitor drugs, was found to work specifically at low concentration (μM) as it is known to suppress the DNA damage response and improves therapeutic response in association with DNA damaging agents but the –SCH 3 group at position 2 in THD induces antipsychotic effect. Hence, the synthesis of a drug which is more potent than THD such as N- substituted phenothiazine and derivatives thereof, using simple and economic process steps is required that could possibly identify the role of TLK1/1B mediated pathway and its significance in DNA damage and chromatin assembly is provided. 

 
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