Journal of Biomolecular Structure & Dynamics最新文献

{"title":"Investigation of the mutated antimicrobial peptides to inhibit ACE2, TMPRSS2 and GRP78 receptors of SARS-CoV-2 and angiotensin II type 1 receptor (AT1R) as well as controlling COVID-19 disease.","authors":"Fatemeh Abedi Dorcheh, Negar Balmeh, Seyed Hossein Hejazi, Najaf Allahyari Fard","doi":"10.1080/07391102.2023.2292307","DOIUrl":"10.1080/07391102.2023.2292307","url":null,"abstract":"<p><p>SARS-CoV-2 is a global problem nowadays. Based on studies, some human receptors are involved in binding to SARS-CoV-2. Thus, the inhibition of these receptors can be effective in the treatment of Covid-19. Because of the proven benefits of antimicrobial peptides (AMPs) and the side effects of chemical drugs, they can be known as an alternative to recent medicines. RCSB PDB to obtain PDB id, StraPep and PhytAMP to acquire Bio-AMPs information and 3-D structure, and AlgPred, Toxinpred, TargetAntiAngio, IL-4pred, IL-6pred, ACPred and Hemopred databases were used to find the best score peptide features. HADDOCK 2.2 was used for molecular docking analysis, and UCSF Chimera software version 1.15, SWISS-MODEL and BIOVIA Discovery Studio Visualizer4.5 were used for mutation and structure modeling. Furthermore, MD simulation results were achieved from GROMACS 4.6.5. Based on the obtained results, the Moricin peptide was found to have the best affinity for ACE2. Moreover, Bacteriocin leucocin-A had the highest affinity for GRP78, Cathelicidin-6 had the best affinity for AT1R, and Bacteriocin PlnK had the best binding affinity for TMPRSS2. Additionally, Bacteriocin glycocin F, Bacteriocin lactococcin-G subunit beta and Cathelicidin-6 peptides were the most common compounds among the four receptors. However, these peptides also have some side effects. Consequently, the mutation eliminated the side effects, and MD simulation results indicated that the mutation proved the result of the docking analysis. The effect of AMPs on ACE2, GRP78, TMPRSS2 and AT1R receptors can be a novel treatment for Covid-19.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1641-1664"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering the structural stability of <i>Magnaporthe oryzae</i> effectors: a secretome-wide <i>in silico</i> analysis.","authors":"Anwesha Chakraborty, Afzal Hussain, Nazmiara Sabnam","doi":"10.1080/07391102.2023.2292795","DOIUrl":"10.1080/07391102.2023.2292795","url":null,"abstract":"<p><p>Rice blast, caused by the ascomycete fungus <i>Magnaporthe oryzae,</i> is a deadly disease and a major threat to global food security. The pathogen secretes small proteinaceous effectors, virulence factors, inside the host to manipulate and perturb the host immune system, allowing the pathogen to colonize and establish a successful infection. While the molecular functions of several effectors are characterized, very little is known about the structural stability of these effectors. We analyzed a total of 554 small secretory proteins (SSPs) from the <i>M. oryzae</i> secretome to decipher key features of intrinsic disorder (ID) and the structural dynamics of the selected putative effectors through thorough and systematic <i>in silico</i> studies. Our results suggest that out of the total SSPs, 66% were predicted as effector proteins, released either into the apoplast or cytoplasm of the host cell. Of these, 68% were found to be intrinsically disordered effector proteins (IDEPs). Among the six distinct classes of disordered effectors, we observed peculiar relationships between the localization of several effectors in the apoplast or cytoplasm and the degree of disorder. We determined the degree of structural disorder and its impact on protein foldability across all the putative small secretory effector proteins from the blast pathogen, further validated by molecular dynamics simulation studies. This study provides definite clues toward unraveling the mystery behind the importance of structural distortions in effectors and their impact on plant-pathogen interactions. The study of these dynamical segments may help identify new effectors as well.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1701-1722"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138804095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, spectral characterization, quantum chemical investigation, biological activity of nano-sized transition metal complexes of tridentate 3-mercapto-4H-1,2,4-triazol-4-yl-aminomethylphenol Schiff base ligand.","authors":"Waleed M Alamier, Abdel-Nasser M A Alaghaz","doi":"10.1080/07391102.2023.2294171","DOIUrl":"10.1080/07391102.2023.2294171","url":null,"abstract":"<p><p>A tridentate Schiff base ligand, H₂MTIP, was produced by condensing salicylaldehyde with 4-amino-4H-1,2,4-triazole-3-thiol. The ligand was then used to create nanosized complexes of Pt(II), Ni(II), Cu(II), and Pd(II). The complexes have the composition [Pt/Ni/Cu/or Pd(MTIP)(H₂O)], this conclusion is supported by molar conductance, magnetic moments, elemental analyses, spectral analyses. In DFT analysis, the 6-31+ g(d,p) basis set was used to fully optimize the energy with respect to the shapes of Schiff base ligand and metal complexes. Pt(II), Ni(II), Cu(II), and Pd(II) complexes have been assigned square-planar geometries. At the same time, the intense diffraction peaks in X-ray diffractograms show their crystalline features with particle sizes in the nanoscale range. The binding interaction of calf thymus DNA with these metal complexes and their insulin-like activity was examined <i>in vitro</i> by inhibiting α-amylase. The study investigated the in-vitro activity of several complexes and identified Pt(II) complex as the one with the highest activity. The researchers then tested this complex for <i>in-vivo</i> antidiabetic activity in induced diabetic rats using the STZ model, and it significantly lowered blood glucose levels. The antioxidant activity and toxicity level of Pt(II) complex were also excellent, suggesting that it could be a good candidate for further research as a possible diabetes drug.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2138-2158"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138885088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational drug discovery of an inhibitor of APOBEC3B as a treatment for epithelial cancers.","authors":"Dominic A Caputa, Quin P Blankenship, Zachary D Smith, Molly M Huebner, Zoe A Vetter, Richard W Parks, Saul Armendariz Lobera, Emmett M Leddin, Cooper A Taylor, Carol A Parish, Bill R Miller","doi":"10.1080/07391102.2023.2293269","DOIUrl":"10.1080/07391102.2023.2293269","url":null,"abstract":"<p><p>Cancer is one of the leading causes of death in the U.S., and tumorous cancers such as cervical, lung, breast, and ovarian cancers are the most common types. APOBEC3B is a nonessential cytidine deaminase found in humans and theorized to defend against viral infection. However, overexpression of APOBEC3B is linked to cancer in humans, which makes APOBEC3B a potential cancer treatment target through competitive inhibition for several tumorous cancers. Computational studies can help reveal a small molecule inhibitor using high-throughput virtual screening of millions of candidates with relatively little cost. This study aims to narrow the field of potential APOBEC3B inhibition candidates for future <i>in vitro</i> assays and provide an effective scaffold for drug design studies. Another goal of this project is to provide critical amino acid targets in the active site for future drug design studies. This study simulated 7.8 million drug candidates using high-throughput virtual screening and further processed the top scoring 241 molecules from AutoDock Vina, DOCK 6, and <i>de novo</i> design. Using virtual screening, <i>de novo</i> design, and molecular dynamics simulations, a competitive inhibitor candidate was discovered with an average binding free energy score of -46.03 kcal/mol, more than 10 kcal/mol better than the substrate control (dCMP). These results indicate that this molecule (or a structural derivative) may be an effective inhibitor of APOBEC3B and prevent host genome mutagenesis resulting from protein overexpression. Another important finding is the confirmation of essential amino acid targets, such as Tyr250 and Gln213 within the active site of APOBEC3B. Therefore, study used novel computational methods to provide a theoretical scaffold for future drug design studies that may prove useful as a treatment for epithelial cancers.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1955-1968"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design of a multi-epitope vaccine (vme-VAC/MST-1) against cholera and vibriosis based on reverse vaccinology and immunoinformatics approaches.","authors":"Pedro Henrique Marques, Thais Cristina Vilela Rodrigues, Eduardo Horta Santos, Lucas Bleicher, Flavia Figueira Aburjaile, Flaviano S Martins, Carlo Jose Freire Oliveira, Vasco Azevedo, Sandeep Tiwari, Siomar Soares","doi":"10.1080/07391102.2023.2293256","DOIUrl":"10.1080/07391102.2023.2293256","url":null,"abstract":"<p><p>Vibriosis and cholera are serious diseases distributed worldwide and caused by six marine bacteria of the <i>Vibrio</i> genus. Thousands of deaths occur each year due to these illnesses, necessitating the development of new preventive measures. Presently, the existing cholera vaccine demonstrates an effectiveness of approximately 60%. Here we describe a new multi-epitope vaccine, 'vme-VAC/MST-1' based on vaccine targets identified by reverse vaccinology and epitopes predicted by immunoinformatics, two currently effective tools for predicting new vaccines for bacterial pathogens. The vaccine was designed to combat vibriosis and cholera by incorporating epitopes predicted for CTL, HTL, and B cells. These epitopes were identified from six vaccine targets revealed through subtractive genomics, combined with reverse vaccinology, and were further filtered using immunoinformatics approaches based on their predicted immunogenicity. To construct the vaccine, 28 epitopes (24 CTL/B and 4 HTL/B) were linked to the sequence of the cholera toxin B subunit adjuvant<i>. In silico</i> analyses indicate that the resulting immunogen is stable, soluble, non-toxic, and non-allergenic. Furthermore, it exhibits no homology to the host and demonstrates a strong capacity to elicit innate, B-cell, and T-cell immune responses. Our analysis suggests that it is likely to elicit immune reactions mediated through the TLR5 pathway, as evidenced by the molecular docking of the vaccine with the receptor, which revealed high affinity and a favorable reaction. Thus, vme-VAC/MST-1 is predicted to be a safe and effective solution against pathogenic <i>Vibrio</i> spp. However, further experimental analyses are required to measure the vaccine's effects <i>In vivo.</i>Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1788-1803"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discussion on the mechanism of Lingguizhugan Decoction in treating hypertension based on network pharmacology and molecular simulation technology.","authors":"Qi Dong, Yu-Jiao Huang, Zhi-Yu Tao, Han-Yue Huang, Lin-Hui Luo, Ying-Qing Zhang","doi":"10.1080/07391102.2023.2294172","DOIUrl":"10.1080/07391102.2023.2294172","url":null,"abstract":"<p><p>To explore the mechanism of Lingguizhugan Decoction in treating hypertension based on network pharmacology and molecular simulation. The active ingredients and potential targets were screened by the Systematic Pharmacological Analysis Platform of Traditional Chinese Medicine (TCMSP). Hypertension-related targets were obtained from OMIM and GeneCards databases. Common targets between drug and hypertension were screened in the Venny platform. A protein-protein interaction (PPI) network was constructed in the STRING database using intersection targets. Key targets in PPI network were analyzed by Cytoscape. R language program was used for Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, the binding abilities of the main active ingredients to critical targets were verified by molecular simulation. Naringenin, quercetin, kaempferol, and β-sitosterol in Lingguizhugan Decoction, and potential targets such as STAT3, AKT1, TNF, IL6, JUN, PTGS2, MMP9, CASP3, TP53, and MAPK3, were screened out. KEGG Enrichment analysis revealed that the common targets of Lingguizhugan Decoction and hypertension are mainly involved in the lipid and atherosclerosis signaling pathway, AGE-RAGE signaling pathway in diabetic complications, fluid shear stress and atherosclerosis, and IL17 signaling pathway. The molecular simulation results showed that naringenin-MAPK3, quercetin-MMP9, quercetin-PTGS2, and quercetin-TP53 were the top four in the docking scores. Naringenin-MAPK3 and quercetin-MMP9 were stable, with binding free energies of -27.97 ± 1.41 kcal/mol and -21.15 ± 3.17 kcal/mol, respectively. The possible mechanism of Lingguizhugan Decoction in treating hypertension is characterized of multi-component, multi-target, and multi-pathway.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2159-2170"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organotin(IV) derivatives of 4-chloro-2-methylphenoxyacetic acid: synthesis, spectral characterization, X-ray structures, anticancer, enzyme inhibition, antileishmanial, antimicrobial and antioxidant activities.","authors":"Shahnaz Rahim, Abdul Sadiq, Aneela Javed, Niaz Muhammad, Mohammed Rafi Shaik, Mohamed E Assal, Maciej Kubicki, Khurshid Ayub, Nighat Fatima, Ali Haider, Sabahat Habib, Sehrish Sarfaraz, Saqib Ali","doi":"10.1080/07391102.2024.2438362","DOIUrl":"10.1080/07391102.2024.2438362","url":null,"abstract":"<p><p>Four organotin(IV) carboxylate complexes; (C₄H₉)₃SnL (<b>1</b>), CH₃SnL (<b>2</b>), (C₄H₉)₂SnL₂ (<b>3</b>) and (CH₃)₂SnL₂ (<b>4</b>) are synthesized by the condensation reaction of organotin(IV) chlorides with sodium-4-chloro-2-methylphenoxyacetate (<b>NaL</b>). The FT-IR spectra suggested bridging/chelating bidentate coordination of the ligand to the tin atom. Single-crystal XRD analysis authenticated the FT-IR findings for <b>1</b> and <b>2</b>. The NMR study has shown no significant differences in the signals of the free and coordinated ligand except for absence of a proton and up-filed/down-field shift of the C signal of the carboxyl group in the spectra. Complexes <b>1</b>-<b>4</b> have shown better enzyme inhibition, antioxidant, antimicrobial, and anticancer activities compared to the free ligand acid. Complex <b>3</b> was the most active inhibitor of AChE, BChE, α-glucosidase and α-amylase with IC₅₀ values of 43.76, 102.39, 232.71 and 91.84 µg/mL, respectively. Additionally, <b>3</b> with IC₅₀ values of 7.52 and 8.77 µg/mL in the DPPH and ABTS assays, respectively was better antioxidant than the standard. Complex <b>4</b> was the most efficient inhibitor of MAO-B and COX-2 enzymes with IC₅₀ values of 106.99 and 12.98 µg/mL, respectively, while <b>1</b> (IC₅₀ = 38.97 µg/mL) has shown the highest 5-LOX inhibition potential. Complexes <b>1</b>-<b>4</b> with IC₅₀ values in the range 237.51-168.35 µg/mL have shown better antileishmanial activity than <b>HL</b> (IC₅₀ = 277.57 µg/mL). The compounds showed good to potent antiproliferative activity in malignant glioma U87 cells with IC₅₀ values in the range 12.54 ± 0.05 to 37.65 ± 0.04 µg/mL. Antimicrobial activities have shown promising results for the compounds compared to the standards in some cases.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2171-2186"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In silico</i> approach reveals <i>N</i>-(5-phenoxythiophen-2-yl)-2-(arylthio)acetamides as promising selective SIRT2 inhibitors: the case of structural optimization of virtual screening-derived hits.","authors":"Mahmut Gozelle, Filiz Bakar-Ates, Alberto Massarotti, Erva Ozkan, Habibe Beyza Gunindi, Yesim Ozkan, Gokcen Eren","doi":"10.1080/07391102.2023.2293252","DOIUrl":"10.1080/07391102.2023.2293252","url":null,"abstract":"<p><p>Epigenetic modifications play an essential role in tumor suppression and promotion. Among the diverse range of epigenetic regulators, SIRT2, a member of NAD⁺-dependent protein deacetylates, has emerged as a crucial regulator of cellular processes, including cell cycle progression, DNA repair, and metabolism, impacting tumor growth and survival. In the present work, a series of <i>N</i>-(5-phenoxythiophen-2-yl)-2-(arylthio)acetamide derivatives were identified following a structural optimization of previously reported virtual screening hits, accompanied by enhanced SIRT2 inhibitory potency. Among the compounds, <b>ST44</b> and <b>ST45</b> selectively inhibited SIRT2 with IC₅₀ values of 6.50 and 7.24 μM, respectively. The predicted binding modes of the two compounds revealed the success of the optimization run. Moreover, <b>ST44</b> displayed antiproliferative effects on the MCF-7 human breast cancer cell line. Further, the contribution of SIRT2 inhibition in this effect of <b>ST44</b> was supported by western blotting, affording an increased α-tubulin acetylation. Furthermore, molecular dynamics (MD) simulations and binding free energy calculations using molecular mechanics/generalized born surface area (MM-GBSA) method evaluated the accuracy of predicted binding poses and ligand affinities. The results revealed that <b>ST44</b> exhibited a remarkable level of stability, with minimal deviations from its initial docking conformation. These findings represented a significant improvement over the virtual screening hits and may contribute substantially to our knowledge for further selective SIRT2 drug discovery.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"1756-1767"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetyl barlerin from <i>Barleria trispinosa</i> induces chemopreventive NQO1 and attenuates LPS-induced inflammation: <i>in vitro</i> and molecular dynamic studies.","authors":"Hamza M Assiry, Ahmed R Hamed, Gamal A Mohamed, Sabrin R M Ibrahim, Abdulrahman E Koshak, Azizah M Malebari, Sana A Fadil, Hossam M Abdallah","doi":"10.1080/07391102.2023.2293272","DOIUrl":"10.1080/07391102.2023.2293272","url":null,"abstract":"<p><p>Extraction and fractionation of <i>Barleria trispinosa</i> growing in Saudi Arabia yielded four iridoid compounds identified by spectroscopic techniques as acetylbarlerin (<b>1</b>), barlerin (<b>2</b>), shanzhiside methyl ester (<b>3</b>) and 6-⍺-L-rhamnopyranosyl-8-O-acetylshanzihiside methyl ester (<b>4</b>). Preliminary experiments confirmed that compound <b>1</b> acts as an inducer of chemopreventive NAD(P)H:Quinone oxidoreductase 1 (NQO1) enzymatic activity in a murine hepatoma (Hepa1c1c7) chemoprevention model. It also demonstrated the ability to inhibit the lipopolysaccharides (LPS)-induced nitric oxide (NO) production in the RAW264.7 macrophage model. Western blotting revealed the ability of compound <b>1</b> to up-regulate the protein expression of the NQO1 marker. Furthermore, compound <b>1</b> elicited NO suppression in RAW264.7 macrophages by inhibiting iNOS protein expression. Molecular docking and molecular simulation studies of <b>1</b> supported its experimental results as an inhibitor of the nuclear factor erythroid 2-Kelch-like ECH-associated protein 1 (Nrf2-KEAP1) complex, resulting in Nrf2-mediated induction of chemopreventive NQO1.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2002-2013"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New nicotinamide derivatives as potential anticancer agents targeting VEGFR-2: design, synthesis, <i>in vitro</i>, and <i>in silico</i> studies.","authors":"Reda G Yousef, Ibrahim H Eissa, Hazem Elkady, Wagdy M Eldehna, Ahmed B M Mehany, Ahmed Nabeeh, Ibrahim M Ibrahim, Alaa Elwan, Mohamed Ayman El-Zahabi","doi":"10.1080/07391102.2023.2294170","DOIUrl":"10.1080/07391102.2023.2294170","url":null,"abstract":"<p><p>Herin, new nicotinamide candidates were designed and synthesized as VEGFR-2 inhibitors. <i>In vitro</i> antiproliferative activities were assessed against MCF-7, HepG-2 and HCT-116 cancer cell lines. The top cytotoxic members <b>15a</b>, <b>15b</b>, <b>16, 18a</b>, and <b>18b</b> were estimated against their selected target (VEGFR-2). Further mechanistic tests were studied for the most potent cytotoxic candidate <b>18a</b>, these studies revealed the ability of compound <b>18a</b> to hinder the progression of HCT-116 cells at S and Pre-G1phases besides boosting early and late apoptosis. Also compound <b>18a</b> was found to significantly decrease the levels immunomodulatory proteins TNF-α and IL-6 while showing a four-fold rise in an apoptotic marker caspase-3 when compared to control cells. The therapeutic index of the designed derivatives was evaluated by computational ADMET and toxicity calculations as well as their potentiality to occupy the VEGFR-2 active site was signposted by molecular docking assessments. Finally, molecular dynamic simulation studies of compound <b>18a</b>-VEGFR-2 complex indicated the high steadiness of compound <b>18a</b> in the VEGFR-2 active site. This study presents compound <b>18a</b> as a lead candidate that can be optimized to get a strong VEGFR-2 inhibitor.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2120-2137"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}