Facile Synthesis, Inhibition of VEGFR-2, Anticancer activity, Molecular Dynamics Simulation and Target Identification of Some New Pyrano thiazine derivatives

Elserwy, Walaa Salah; Mohammed, Neama; Elserwy, Weam Salah; Abdallah, Mohamed; El-Rashedy, Ahmed

doi:10.21608/ejchem.2022.173057.7167

Facile Synthesis, Inhibition of VEGFR-2, Anticancer activity, Molecular Dynamics Simulation and Target Identification of Some New Pyrano thiazine derivatives

Document Type : Original Article

Authors

¹ Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Cairo, Egypt, 12622.

² Department Of Microbial and Natural Products chemistry, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Cairo, Egypt, 12622.

³ Atos Pharma, Elkatyba Land, Belbis, ElSharkya 44621, Egypt.

10.21608/ejchem.2022.173057.7167

Abstract

A new series of )2-amino-4-(substituted)-4,10-dihydrobenzo[b]pyrano[2,3-e][1,4]thiazine-3-carbonitrile( 3(a, b) was synthesized by the reaction of 2-(substituted) malononitrile with 2H-benzo[b][1,4]thiazin-3(4H)-one as a key starting material, )2-amino-4-(substituted)-4,10-dihydrobenzo[b]pyrano[2,3-e][1,4]thiazine-3-carbonitrile( 3(a, b) reacted with some reagents, namely, formic acid, sulphuric acid, thiosemicarbazide, ethyl acetoacetate, triethyl orthoformate, carbon disulphide, diethylmalonate, malononitrile, phosphoryl chloride , and acetic anhydride to produce compounds 4(a,b), 5(a,b), 6(a,b), 8(a,b), 9(a,b), 10(a,b),11(a,b),14(a,b),15(a,b), and 18(a,b) some of newly synthesized compounds were studied and screened for their in vitro anticancer activity. Moreover, molecular dynamics simulation and target identification studies were conducted to support the findings .All the newly synthesized compounds were structurally confirmed by various modern analytical methods (IR, 1H NMR and MS).

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