In silico Design, Synthesis and Biological Evaluation of Novel Thieno[3,2‐d]pyrimidine Derivatives for Cancer Therapy – A Preliminary Study on the Inhibitory Potential towards ATR Kinase Domain and PIKK Family

Author:

Sirakanyan Samvel N.1,Dilip Haritha2,Geronikaki Athina3ORCID,Spinelli Domenico4,Kirubakaran Sivapriya2,Petrou Anthi3,Hakobyan Elmira K.1,Kartsev Victor G.5,Paronikyan Ervand G.1,Yegoryan Hasmik A.1,Yermalovyan Lilit V.1,Hovakimyan Anush A.1

Affiliation:

1. Scientific Technological Center of Organic and Pharmaceutical Chemistry of National Academy of Science of Republic of Armenia Institute of Fine Organic Chemistry of A.L.Mnjoyan, Ave. Azatutyan 26 Yerevan 0014 Armenia

2. Department of Chemistry Indian Institute of Technology Gandhinagar, Palaj Village Gandhinagar Gujarat 382055 India

3. School of Pharmacy Aristotle University of Thessaloniki 54124 Thessaloniki Greece

4. Dipartimento di Chimica G. Ciamician Alma Mater Studiorum-Università di Bologna Via F. Selmi 2 40126 Bologna Italy

5. InterBioScreen Moscow 119019 Russia

Abstract

AbstractContinuing our studies in the field of new heterocyclic compounds with biological interest, herein we report the synthesis and anticancer activity of new N‐ and S‐substituted derivatives of tetracyclic pyrido[3′,2′ : 4,5]thieno[3,2‐d]pyrimidines. In this regard, starting from the thieno[2,3‐b]pyridine‐2‐carboxylates, the corresponding 8(9)‐aminopyrido[3′,2′ : 4,5]thieno[3,2‐d]pyrimidin‐7(8)‐ones, as well as chloro derivatives were obtained. Based on the latter, amino, hydrazino and S‐alkyl derivatives of pyrido[3′,2′ : 4,5]thieno[3,2‐d]pyrimidines were synthesized subsequently. The current study focuses on identifying the potential of thieno[3,2‐d]pyrimidine derivatives primarily towards ATR kinase inhibition, through computational predictions, followed by synthesis and cancer cell viability studies, along with an aim to develop the core as PIKK inhibitors for cancer therapy.

Funder

Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja

Publisher

Wiley

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