BMC Chemistry最新文献

{"title":"Solidified reverse micellar solution-based chitosan-coated solid lipid nanoparticles as a new approach to enhance oral delivery of artemether in malaria treatment","authors":"Franklin Chimaobi Kenechukwu,&nbsp;Kingsley Chinazam Ugwu,&nbsp;Chibuzor Stanley Offorbuike,&nbsp;Enyi Moses Ojukwu,&nbsp;Thaddeus Harrison Gugu,&nbsp;Reuben Ejike Eze,&nbsp;Chinazom Precious Agbo,&nbsp;Mumuni Audu Momoh,&nbsp;Anthony Ikechukwu Onah,&nbsp;Chinekwu Sherridan Nwagwu,&nbsp;Onyinyechi Lydia Ugorji,&nbsp;Emmanuel Chekwube Ossai,&nbsp;Calister Elochukwu Ugwu,&nbsp;Paul Achile Akpa,&nbsp;Adaeze Chidiebere Echezona,&nbsp;Samuel WisdomofGod Uzondu,&nbsp;Chimaobi Odinaka Ugorji,&nbsp;Wilfred Ikechukwu Ugwuoke,&nbsp;Teerapol Srichana,&nbsp;Anthony Amaechi Attama","doi":"10.1186/s13065-025-01422-4","DOIUrl":"10.1186/s13065-025-01422-4","url":null,"abstract":"<div><p>Solidified reverse micellar technology and surface-modification are promising techniques for improving the biopharmaceutical properties of poorly water-soluble drugs such as artemether, a first-line antimalarial drug. Thus, the aim of this study was to develop and evaluate artemether-loaded chitosan-coated solid lipid nanoparticles (SLNs) based on solidified reverse micellar solution (SRMS) for improved oral malaria therapy. Artemether-loaded and unloaded SLNs were prepared from optimized SRMS (consisting of Phospholipon^® 90G and Compritol^® ATO 888 at 3:7 ratio) with or without chitosan by high-shear melt-homogenization, and thereafter characterized for physicochemical performance, stability, safety and antimalarial activity using <i>Plasmodium berghei</i>-infected mice. Results showed both smooth and irregular particles with a layer of polymer coating in chitosan-modified SLNs, increased drug amorphization as well as compatibility of the drug and excipients employed in the formulations. The optimized formulation was stable and nanomeric (size 292.90 ± 5.01 nm, polydispersity index 0.191 ± 0.09, and zeta-potential + 32.50 ± 1.58 mV) with good encapsulation efficiency (82.03%), demonstrated minimal toxicity on Caco-2 cells, exhibited controlled drug release compared with fast release of artemether suspension and gave significantly (p &lt; 0.05) greater antimalarial activity than artemether suspension. Artemether-loaded chitosan-coated SRMS-based SLNs improved the antimalarial activity of the drug and can be pursued as a novel alternative for improved oral malaria treatment.</p></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01422-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stability-indicating spectrophotometric manipulations for the determination of Letrozole in the presence of its alkali-induced degradation products; towards whiteness and ChlorTox scale perspectives","authors":"Nourhan A. Abd El-Fatah,&nbsp;Manal Mohammed Fouad,&nbsp;Maha A. Hegazy,&nbsp;Ghada M. El-Sayed","doi":"10.1186/s13065-025-01416-2","DOIUrl":"10.1186/s13065-025-01416-2","url":null,"abstract":"<div><p>Letrozole (LTZ) is an established first hormonal treatment for breast cancer, yet it was found to be highly susceptible for degradation in alkaline medium due to the presence of cyano phenyl group. Consequently, three stability-indicating spectrophotometric manipulations for LTZ quantification in presence of its alkali-induced degradation products were developed for the first time; ensuring methods’ simplicity, sensitivity and accuracy. The first method was <i>Second derivative (D</i>_<i>2</i><i>)</i> by recording peak amplitude of the drug at 226.8 nm. The second method was <i>Ratio difference (RD)</i> where the peak amplitude were recorded at wavelengths 240.0 nm and 258.0 nm. The third method was <i>First derivative of ratio spectra (DD</i>_<i>1</i><i>)</i> through recording peak amplitude at 246.0 nm. Linearity ranged from 1.00 to 16.00 µg/mL for D₂, while from 3.00 to 16.00 µg/mL for RD and DD₁ with adequate recoveries 100.02 ± 1.371, 100.05 ± 1.972 and 100.40 ± 1.223 for D₂, RD and DD₁, respectively. The proposed methods were validated as per ICH guidelines, and were successfully applied for determination of LTZ in bulk powder, laboratory-prepared mixtures, and pharmaceutical formulation. The Whiteness tool, using the RBG12 algorithm, was employed to evaluate environmental aspects, as well, ChlorTox scale was used to assess chemicals’ hazards for this study.</p></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01416-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, and antibacterial activities of novel 1,3,4a,9-tetraza-4H-fluoren-2-amines incorporating phenoxy-N-arylacetamide, pyrazole, and 2-(4-(1-phenyl-1H-pyrazol-3-yl)phenoxy)-N-arylacetamide moieties","authors":"Reham E. Abdelwahab,&nbsp;Ahmed H. M. Elwahy,&nbsp;Nada S. Ibrahim,&nbsp;Amr M. Abdelmoniem,&nbsp;Ismail A. Abdelhamid","doi":"10.1186/s13065-025-01421-5","DOIUrl":"10.1186/s13065-025-01421-5","url":null,"abstract":"<div><p>A ring annelation reaction was used to successfully prepare benzo[4,5]imidazo[1,2-<i>a</i>][1,3,5]triazines (Systematic Name: 1,3,4a,9-tetraza-4<i>H</i>-fluoren-2-amines) tethered to phenoxy-<i>N</i>-arylacetamide, pyrazole, and 2-(4-(1-phenyl-1<i>H</i>-pyrazol-3-yl)phenoxy)-<i>N</i>-arylacetamide moieties utilizing 1-(1<i>H</i>-benzo[<i>d</i>]imidazol-2-yl)guanidine and the proper aldehydes as precursors. 2-(Phenylamino)ethyl fragment of compound <b>7</b> was cleaved off and compound <b>8</b> was formed. The constitutions of the novel compounds were confirmed based on spectral data. The antibacterial activity was evaluated for the prepared compounds against two gram-negative and two gram-positive bacteria. Among them, compound <b>12b</b> (inhibition zone 16 ± 0.7 mm) was the most promising against <i>S. aureus</i> compared to Gentamycin (15 ± 0 mm). Also, compounds <b>5a</b> and <b>5d</b> exerted comparable antibacterial activity (inhibition zones 13 ± 1.4 and 13 ± 2.1 mm), respectively to Gentamycin against <i>S. aureus</i>. Minimum inhibitory concentration (MIC) evaluation against <i>S. aureus</i> showed that compound <b>12b</b> had the lowest MIC value (78.1 µg/mL).</p></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01421-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Label-free upconversion nanosensor for water safety monitoring of permanganate and dichromate ions","authors":"Kuncheng Xu,&nbsp;Hongli Wen,&nbsp;Wei Song,&nbsp;Abdur Raheem Aleem,&nbsp;Murugavelu Marimuthu,&nbsp;Wang Chen,&nbsp;Qiuqiang Zhan,&nbsp;Deshmukh Abdul Hakeem,&nbsp;Saleh T. Mahmoud","doi":"10.1186/s13065-025-01415-3","DOIUrl":"10.1186/s13065-025-01415-3","url":null,"abstract":"<div><p>Water contaminated with heavy metal ions poses serious threat to the human health and environment protection. It is imperative to develop analytical tools to detect heavy metal ions. Herein, we propose autofluorescence free SiO₂ modified upconversion nanosensor for label-free and fast determination of MnO₄⁻ and Cr₂O₇²⁻ anions. The highly efficient and multi-colour upconversion luminescence (UCL) of UCNPs@SiO₂ was effectively quenched by MnO₄⁻ and Cr₂O₇²⁻ anions with fast response time of 2 and 1 min, respectively. The UCNPs@SiO₂ nanosensor exhibits linear detection ranges of 0.6–2000, 2–2000 µM with the LOD at 0.15, 0.04 µM for MnO₄⁻ and Cr₂O₇²⁻ anions, respectively. The nanosensor was successfully applied for real lake and tap water samples with satisfactory results. The UCNPs@SiO₂ UCL nanosensor demonstrates autofluorescence free and fast determination of MnO₄⁻ and Cr₂O₇²⁻ anions with high sensitivity, good specificity, low LOD, and wide linear detection range, holding great potential for food and environmental sample sensing.</p></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01415-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143553669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidencing nickel biosorption capacity of cyanobacteria Chroococcidiopsis sp.: potential metallo-protective agents","authors":"Hadjira Hamai-Amara,&nbsp;Imen Saadaoui,&nbsp;Maroua Cherif,&nbsp;Dana A. Da’ana,&nbsp;Lama Soubra,&nbsp;Mohammad A. Al-Ghouti","doi":"10.1186/s13065-025-01393-6","DOIUrl":"10.1186/s13065-025-01393-6","url":null,"abstract":"<div><p>The increasing prevalence of toxic elements such as nickel (Ni) in the environment poses a significant threat to human health due to its carcinogenic effect. The study investigates the Ni biosorption potential of three cyanobacteria strains: <i>Euhalothece sp., Halospira sp.</i>, and <i>Chroococcidiopsis sp.</i> Hence, the physicochemical properties of biomass and extract were assessed through transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and Brunauer-Emmet-Teller (BET). Batch experiments for Ni²⁺ biosorption were conducted and residual nickel (Ni²⁺) levels were quantitatively assessed using Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES). The results evidence interesting Ni²⁺ removal efficiency of <i>Chroococcidiopsis sp.</i> biomass reaching a biosorption capacity of 18.19 mg g⁻¹ under pH 6, and 37 °C. Several functional groups including amide, carbonyl, phosphate, and carboxyl groups were revealed as key players in this process via FTIR. Finally, such findings highlight the significant potential of cyanobacterial biomass and by-products to reduce nickel bioavailability to prevent Ni-induced carcinogenesis.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01393-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143553671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two birds with one stone: sustainable smart spectrophotometric methods for concurrent determination of silodosin and mirabegron: application to dosage forms and greenness assessment","authors":"Khalid M. Badr El-Din,&nbsp;Sayed M. Derayea,&nbsp;Ahmed S. Ahmed,&nbsp;Mohamed Oraby,&nbsp;Mohamed A. Abdelshakour","doi":"10.1186/s13065-025-01411-7","DOIUrl":"10.1186/s13065-025-01411-7","url":null,"abstract":"<div><p>A new combination of silodosin and mirabegron has recently obtained approval in the Indian market for addressing the benign prostatic hyperplasia symptoms associated with overactive bladder syndrome. In this study, we present four validated UV-spectrophotometric methods that rely on straightforward mathematical calculations for the quick and simultaneous assay of MRB and SLD in commercial tablets and synthetic mixes without the need for prior separation. The suggested methods include dual-wavelength, induced dual-wavelength, ratio difference, and area under the curve. These methods were effectively used to determine SLD and MRB simultaneously in combinations with severe spectrum overlap, showing excellent recoveries free from interference from pharmaceutical excipients. The proposed approaches were assessed and validated following the guidelines set forth by the International Conference for Harmonization (ICH). The methods exhibited linear ranges of 1–20 μg mL⁻¹ and 1–25 μg mL⁻¹ for SLD and MRB, respectively. Their environmental friendliness was assessed using the Analytical Greenness Calculator (AGREE) and The Green Analytical Procedure Index (GAPI) tools, demonstrating their supremacy in terms of greenness compared to the reported chromatographic method. There were no appreciable variations in accuracy or precision between the reported chromatographic method and statistical comparisons based on t- and F values. Consequently, these suggested methods are deemed effective in routine analysis of SLD and MRB, serving as cost-effective alternatives in quality control laboratories lacking expensive chromatographic instruments.</p></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01411-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanao/organocatalyat SiO2/4-(2-Aminoethyl)-morpholine as a new, reusable, and efficacious catalyst for the synthesis of polyhydroquinolines derivatives and antibacterially active evaluation","authors":"Leila Amiri-Zirtol,&nbsp;Zahra Karimi,&nbsp;Javad Farahbakhsh,&nbsp;Ahmad Gholami,&nbsp;Seyedeh Narjes Abootalebi","doi":"10.1186/s13065-025-01403-7","DOIUrl":"10.1186/s13065-025-01403-7","url":null,"abstract":"<div><p>In this study, a new nanocomposite comprising 4-(2-Aminoethyl)-morpholine, an organic catalyst, was prepared on the surface of silica. The absence of metal in the catalyst structure contributes to its environmental friendliness. This novel nanocatalyst was used for multi-component reactions (MCRs). Having a nano size for the composite enhances the contact between the raw materials and the catalytic surface, leading to significant advancement in the reaction. The synthesized composite was identified and evaluated using FT-IR, EDX, EDX-Mapping, TGA, XRD, BET, TEM, and FE-SEM analysis. The characteristic analysis confirmed the synthesis of both nano-silica/4-(2-Aminoethyl)-morpholine catalyst and polyhydroquinoline. The composite’s catalytic properties for synthesizing some polyhydroquinoline derivatives were investigated, yielding promising and remarkable results with high 95% yields and short reaction times. The antibacterial properties of the synthesized compounds were also examined against four types of pathogenic bacteria. The highest inhibitory effect was attributed to the compound Ethyl-4-(3-hydroxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate exhibited the highest antibacterial properties.</p></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01403-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A green three-ratio manipulating spectrophotometric approaches for the determination of a binary mixture of pantoprazole and domperidone","authors":"Hamed H. M. Abuseada,&nbsp;Osama I. Abdel Sattar,&nbsp;Ahmed W. Madkour,&nbsp;Ahmed S. Taha","doi":"10.1186/s13065-025-01414-4","DOIUrl":"10.1186/s13065-025-01414-4","url":null,"abstract":"<div><h3>Background</h3><p>Pantoprazole (PAN) is a proton pump inhibitor used to treat GERD and hyperacidity by suppressing gastric acid secretion, effectively relieving symptoms such as heartburn, acid regurgitation, and indigestion. Domperidone (DOM) is a prokinetic agent that enhances gastrointestinal motility, helping to alleviate nausea, vomiting, and bloating caused by motility disorders. Their combination (Pantosec-D) provides rapid and comprehensive relief from both acid-related and motility-related symptoms, significantly improving patient comfort and quality of life.</p><h3>Objective</h3><p>This study aims to develop and validate three eco-friendly spectrophotometric techniques—ratio difference (RD), first derivative (1DD), and mean centering (MC) of ratio spectra—for the simultaneous determination of PAN and DOM in pharmaceutical formulations.</p><h3>Method</h3><p>The proposed methods resolve spectral overlap through ratio spectra manipulation. In the RD method, DOM is quantified by measuring the amplitude difference at 209 nm and 233 nm, while PAN is determined at 254 nm and 223 nm. The ¹DD method detects DOM at 215 nm and PAN at 249 nm, whereas the MC method quantifies PAN at 254 nm and DOM at 209 nm.</p><h3>Results</h3><p>The suggested methods were validated according to ICH regulations. Pharmaceutical formulations comprising PAN and DOM were effectively analyzed using the linear correlations obtained for both drugs over concentration ranges of 0.5–52 µg/mL and 1–18 µg/mL, respectively.</p><h3>Conclusion</h3><p>Compared with reported spectrophotometric techniques, ratio methods are especially beneficial for routine pharmaceutical analysis due to their ease of use, capacity for handling overlapping spectra, and robustness to experimental variations. Compared with reported chromatographic methods, these techniques provide easy-to-use, reasonably priced, less solvent, and dependable substitutes for the standard quality control of these medications in pharmaceutical dosage forms.</p></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01414-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green stability-indicating RP-HPTLC approach for determining suvorexant in commercial tablet dosage forms","authors":"Prawez Alam,&nbsp;Faiyaz Shakeel,&nbsp;Mohammed H. Alqarni,&nbsp;Ahmed I. Foudah,&nbsp;Tariq M. Aljarba,&nbsp;Fatma M. Abdel Bar,&nbsp;Mohd Imran,&nbsp;Mohammad Ali","doi":"10.1186/s13065-025-01431-3","DOIUrl":"10.1186/s13065-025-01431-3","url":null,"abstract":"<div><p>A novel sedative/hypnotic drug called suvorexant (SUV) is advised for treating insomnia. From a forensic standpoint, it is important medicine because of its sedative/hypnotic and depressing effects. There are no green “high-performance thin-layer chromatographic (HPTLC)” techniques for measuring SUV in the literature. Therefore, this study aims to develop and validate a reverse-phase HPTLC approach that indicates green stability for SUV measurement in commercially available tablet dosage forms. SUV was detected at 255 nm in wavelength. The suggested SUV analysis approach’s greenness was assessed using the “analytical eco-scale (AES), ChlorTox, and analytical GREEnness (AGREE)” tools. The current SUV analysis method showed linearity in the 10–1200 ng/band range. Furthermore, the SUV analytical method was robust, accurate (% recoveries = 98.18–99.30), sensitive (LOD = 3.32 ng/band and LOQ = 9.98 ng/band), precise (% CV = 0.78–0.94), and environmentally friendly. The “AES, total ChlorTox, and AGREE” scales were derived to be 93, 0.96 g, and 0.88, respectively, using the current SUV analytical method, demonstrating an exceptional greenness profile. SUV was shown to be suitably unstable under oxidative degradation conditions and suitably stable under acid, base, and heat degradation conditions. Furthermore, the SUV analytical method’s stability-indicating component identified SUV in the presence of its breakdown products. It was observed that marketed SUV tablet brands A and B contained, respectively, 98.18 and 101.32% of SUV. The findings of the study indicated that SUV in marketed tablet dosage forms may be monitored on a regular basis with the use of the current green HPTLC methodology.</p></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01431-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico discovery of a novel potential allosteric PI3Kα inhibitor incorporating 2-oxopropyl urea targeting head and neck squamous cell carcinoma","authors":"Wenqing Jia,&nbsp;Guangzhuang Li,&nbsp;Xianchao Cheng,&nbsp;Ruijie Zhang,&nbsp;Yukui Ma","doi":"10.1186/s13065-025-01420-6","DOIUrl":"10.1186/s13065-025-01420-6","url":null,"abstract":"<div><p>Head and neck squamous cell carcinoma (HNSCC) is the most common head and neck cancer and highly aggressive and heterogeneous. Targeted therapy is still the main treatment method used in clinic due to lower side effect and personalized medication. In order to discover novel and effective drugs with low side effect against HNSCC, we analyzed the genes related to HNSCC, and found that <i>PIK3CA</i> was highly expressed in tumor tissues and often experienced mutations, leading to excessive activation of phosphoinositide 3-kinase alpha (PI3Kα), promoting the development of HNSCC. The allosteric PI3Kα inhibitor <b>STX-478</b> inhibits the growth of tumor with hotspot mutations in PI3Kα and shows prominent efficacy on the treatment of human HNSCC xenografts without displaying the metabolic dysfunction observed in Alpelisib. These mutations open the allosteric site more readily, increasing the selectivity of <b>STX-478</b> for mutant PI3Kα. <b>STX-478</b> cleverly avoids the side effect of ATP competitive PI3Kα inhibitors. So, the structure of <b>STX-478</b> was optimized based on the interaction mechanism between <b>STX-478</b> and PI3Kα. Then, virtual screening, binding mode research, target verification, physical and chemical properties, pharmacokinetic properties and stabilities of ligand-PI3Kα complexes were evaluated by computer technologies (scaffold hopping, cdocker, SuperPred, SwissTarget prediction, Lipinski’s rule of five, ADMET and MD simulation). Finally, <b>J-53</b> (2-oxopropyl urea compound) with excellent properties was selected. <b>J-53</b> not only formed H-bonds with key amino acids, but its unique -C(O)CH₃ could also form H-bonds with ILE1019, making it more stably bound to PI3Kα and contributing to its activity. After the SciFinder verification, <b>J-53</b> with novel structure had the value of further study. This study suggested that <b>J-53</b> could be used as potential inhibitors of PI3Kα, and provides valuable information for the subsequent drug discovery of allosteric PI3Kα inhibitors.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01420-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}