Design, synthesis and evaluation of novel tetrahydropyridothienopyrimidin-ureas as cytotoxic and anti-angiogenic agents

Motahari, Rasoul; Boshagh, Mohammad Amin; Moghimi, Setareh; Peytam, Fariba; Hasanvand, Zaman; Bakhshaiesh, Tayebeh Oghabi; Foroumadi, Roham; Bijanzadeh, Hamid Reza; Firoozpour, Loghman; Khalaj, Ali; Esmaeili, Rezvan; Foroumadi, Alireza

doi:10.1038/s41598-022-13515-4

Cited by 2 publications

(2 citation statements)

References 39 publications

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“…Thus, a concentration of 100 ng/mL Bevacizumab, 1.6 μM SHP-60, and their combination, which exhibited mild inhibition, and this information was used for subsequent experimental work. The cell viability analysis was carried out using MTT assay which is routinely used for this analysis for the HUVEC cell line and other cells − …”

Section: Resultsmentioning

confidence: 99%

Investigating the Protein-Based Therapeutic Relationship between Honey Protein SHP-60 and Bevacizumab on Angiogenesis: Exploring the Synergistic Effect through In Vitro and In Silico Analysis

Wahid,

Nazeer,

Qadir

et al. 2024

ACS Omega

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Honey is a natural product produced by honeybees, which has been used not only as food but also as a medicine by humans for thousands of years. In this study, 60 kDa protein was purified from Pakistani Sidr honey named as SHP-60 (Sidr Honey Protein-60), and its antioxidant potential and the effect of Bevacizumab with purified protein on in vitro angiogenesis using human umbilical vein endothelial cells (HUVEC) were investigated. We further validated the molecular protein−protein (SHP-60 with Bevacizumab) interactions through in silico analysis. It showed very promising antioxidant activity by reducing 2,2-diphenyl-1-picrylhydrazyl free radicals with a maximum of 83% inhibition at 50 μM and an IC 50 of 26.45 μM statistically significant (**p < 0.01). Angiogenesis is considered a hallmark of cancer, and without it, the tumor cannot grow or metastasize. Bevacizumab, SHP-60, and both in combination were used to treat HUVEC, and the MTT assay was used to assess cell viability. To demonstrate in vitro angiogenesis, HUVEC was grown on Geltrex, and the formation of endotubes was examined using a tube formation assay. HUVEC viability was dose-dependently decreased by Bevacizumab, SHP-60, and both together. Bevacizumab and SHP-60 both inhibited angiogenesis in vitro, and their combination displayed levels of inhibition even higher than those of Bevacizumab alone. We investigated the protein−protein molecular docking interactions and molecular dynamics simulation analysis of MRJP3 (major royal jelly protein 3) similar to SHP-60 in molecular weight with both the heavy chain (HC) and light chain (LC) of Bevacizumab. We found significant interactions between the LC and MRJP3, indicating that ASN468, GLN470, and ASN473 of MRJP3 interact with SER156, SER159, and GLU161 of LC of Bevacizumab. The integration of experimental data and computational techniques is believed to improve the reliability of the findings and aid in future drug design.

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Section: Resultsmentioning

confidence: 99%

Investigating the Protein-Based Therapeutic Relationship between Honey Protein SHP-60 and Bevacizumab on Angiogenesis: Exploring the Synergistic Effect through In Vitro and In Silico Analysis

Wahid,

Nazeer,

Qadir

et al. 2024

ACS Omega

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“…Some of these compounds are summarised in Figure 2. [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] Interestingly, it has been noted that 4-amino substituents, whether aryl/aryl alkyl or urea, play a crucial role in binding to cancer proteins. These findings, particularly regarding the 6-membered ring fused theino [2,3-d]pyridines and their medicinal properties, prompted us to develop a more efficient delivery system for new 4-amino substituted 5,6,7,8tetrahydrobenzo [4,5]thieno [2,3-d]pyrimidines.…”

Section: Synthesismentioning

confidence: 99%

Design and Efficient Synthesis of New 4-Amino-Substituted 2-(4-Bromobenzyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines of Anticancer Interest and Their In Silico Study

Kumar,

Arora,

Thakur

et al. 2024

Synthesis

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Thienopyrimidines are one of the emerging classes among fused pyrimidines owing to their broad spectrum of pharmacological properties, including antimicrobial, anti-inflammatory, antimalarial, anticancer, etc. The anticancer activity of these compounds is mechanistically proven via the inhibition of validated drug targets such as EGFR, VEGFR-2, PI3K, and c-kit. In this research article, we designed and attempted synthesis of new 4-amino substituted 2-(4-bromobenzyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines to explore their anticancer potential further. These heterocycles were designed based on pharmacophoric features of the core heterocycle, varying its C-4 substitution with a variety of amines and considering cancer protein-ligand interactions aiming to get potent lead molecules. The target compound-protein interaction complexes were analyzed, and lead compounds were identified based on their better binding affinity in molecular docking studies.

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Design, synthesis and evaluation of novel tetrahydropyridothienopyrimidin-ureas as cytotoxic and anti-angiogenic agents

Cited by 2 publications

References 39 publications

Investigating the Protein-Based Therapeutic Relationship between Honey Protein SHP-60 and Bevacizumab on Angiogenesis: Exploring the Synergistic Effect through In Vitro and In Silico Analysis

Investigating the Protein-Based Therapeutic Relationship between Honey Protein SHP-60 and Bevacizumab on Angiogenesis: Exploring the Synergistic Effect through In Vitro and In Silico Analysis

Design and Efficient Synthesis of New 4-Amino-Substituted 2-(4-Bromobenzyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines of Anticancer Interest and Their In Silico Study

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