In Silico Evaluation of a Promising Key Intermediate Thieno [2,3-d] Pyrimidine Derivative with Expected JAK2 Kinase Inhibitory Activity

Abstract

This work describes the synthesis and the cytotoxic evaluation of thiophene and thienopyrimidine derivatives. The investigated compound was subjected to target prediction that indicated its high affinity to kinases and to Janus kinase 2 (JAK2) specifically. Molecular docking screening was performed on three different JAK2 proteins downloaded from the Protein Data Bank (PDB: 5AEP, 4C62 and 3ZMM). In vitro kinase inhibitory activity was evaluated and then compound cytotoxicity was performed on three different cancerous cell lines (HT-29, HepG-2, and MCF-7). Marked cytotoxic activity of the thienopyrimidine derivative against the HepG-2 cell line was demonstrated, reflected by its IC50 value of 8.001 ± 0.0445 μM, which is better than that of the reference standard (IC50 13.91 ± 2.170 μM). Pharmacokinetic studies revealed good well permeability and GI absorption with no violations against Lipinski’s rule.

Impact of Synthesized Indoloquinoline Analog to Isolates from Cryptolepis sanguinolenta on Tumor Growth Inhibition and Hepatotoxicity in Ehrlich Solid Tumor-Bearing Female Mice

“…Browsed database of the investigated compound was in mdb format. The gradient for energy minimization was 0.05, and MMFF94X was the force field by default [ 21 ].…”

In Silico Screening and Anticancer-Apoptotic Evaluation of Newly Synthesized Thienopyrimidine/Sulfonamide Hybrids

“…According to reported literature [ 30 , 31 ], compounds with a positive drug likeness score are considered good drug candidates. As shown in Table 6 , all the investigated compounds except 3b expressed positive drug likeness values ranging from 0.73 to 1.58, among which the N-carbamimidoylcyclohexathieno[2,3-d]pyrimidine benzenesulfonamide derivative 4ai and Ethyl-4-((4-(N-carbamimidoylsulfamoyl)phenyl)amino)-5-methylthieno[2,3-d]pyrimidine-6-carboxylate 4bi recorded the best scores (1.58 and 1.19, respectively; Figure 7 ).…”

“…According to reported literature [30,31], compounds with a positive drug likeness score are considered good drug candidates. As shown in Table 6, all the investigated compounds except 3b expressed positive drug likeness values ranging from 0.73 to 1.58,…”

Cytotoxic Potential of Novel Quinoline Derivative: 11-(1,4-Bisaminopropylpiperazinyl)5-methyl-5H-indolo[2,3-b]quinoline against Different Cancer Cell Lines via Activation and Deactivation of the Expression of Some Proteins

“…A molecular operating environment (MOE.2014.09) was used to perform molecular docking according to [ 42 ], and caspase-3 protein was downloaded from the protein data bank (pdb: 7JL7) [ 43 ]. Ligand and protein structural optimizations were applied as reported [ 44 , 45 ] by calculating partial charges, 3D protonation, and strands correction followed by energy minimization.…”