BMC Chemistry最新文献

{"title":"Structural insights and ADMET analysis of CAFI: hydrogen bonding, molecular docking, and drug-likeness in renal function enhancers","authors":"P. Divya,&nbsp;V. S. Jeba Reeda,&nbsp;P. Rajkumar,&nbsp;A. Amala Jeya Ranchani,&nbsp;R. Shahidha,&nbsp;Mudassar Shahid,&nbsp;Nazia Siddiqui,&nbsp;Saleem Javed","doi":"10.1186/s13065-025-01383-8","DOIUrl":"10.1186/s13065-025-01383-8","url":null,"abstract":"<div><p>Using quantum chemical calculations, spectroscopic methods, and molecular docking analysis, this work explores the electronic, structural, vibrational, and biological characteristics of CAFI. Intramolecular hydrogen bonding between the methyl and C = O groups (with bond lengths less than 3 Å) was detected, affirming molecular stability. Corresponded with the theoretical expectations, FT-IR and UV spectra corroborating CAFI’s chemical stability. Frontier molecular orbital study indicated HOMO-LUMO energy gaps between 4.227 eV (gas) and 4.792 eV (ethanol), underscoring charge transfer activity. Molecular docking revealed CAFI as the most potent binder to proteins that stimulate kidney function, with a binding energy of -4.08 kcal/mol and sustained hydrogen bonding connections. ADMET analysis confirmed CAFI’s drug-likeness, indicating advantageous absorption, distribution, metabolism, and toxicity characteristics. These findings indicate CAFI as a potential treatment candidate for the regulation of renal function.</p></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01383-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404090","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":"Computational approaches: atom-based 3D-QSAR, molecular docking, ADME-Tox, MD simulation and DFT to find novel multi-targeted anti-tubercular agents","authors":"Debadash Panigrahi,&nbsp;Susanta Kumar Sahu","doi":"10.1186/s13065-024-01357-2","DOIUrl":"10.1186/s13065-024-01357-2","url":null,"abstract":"<div><p>Tuberculosis (TB) has become the biggest threat to human society because of the rapid rise in resistance to the causative bacteria Mycobacterium tuberculosis (MTB) against the available anti-tubercular drugs. There is an urgent need to design new multi-targeted anti-tubercular agents to overcome the resistance species of MTB through computational design tools. With this aim in mind, we performed a combination of atom-based three-dimensional quantitative structure–activity relationship (3D-QSAR), six-point pharmacophore (AHHRRR), and molecular docking analysis on a series of fifty-eight anti-tubercular agents. The created QSAR model had a R² value of 0.9521, a Q² value of 0.8589, and a Pearson r-factor of 0.8988, all of which are statistically significant. This means that the model was effective at making predictions. We performed the molecular docking study for the data set of compounds with the two important anti-tubercular target proteins, Enoyl acyl carrier protein reductase (InhA) (PDBID: 2NSD) and Decaprenyl phosphoryl-β-D-Ribose 20-epimerase (DprE1) (PDBID: 4FDO). We used the similarity search principle to do virtual screening on 237 compounds from the PubChem database in order to find strong anti-tubercular agents that act against multiple targets. The screened compound, MK3, showed the highest docking score of −9.2 and −8.3 kJ/mol towards both the target proteins InhA and DprE1, which were picked for a 100 ns molecular-dynamic simulation study using GROMACS. The data showed that the compound MK3 was thermodynamically stable and effectively bound to both target proteins in their active binding pockets without much movement. The analysis of the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), and energy gap predicts the molecular reactivity and stability of the identified molecule. Based on the result of the above studies, the proposed compound MK3 can be successfully used for the development of a novel multi-targeted anti-tubercular agent with high binding affinity and favourable ADME-T properties.</p></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-024-01357-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404089","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":"Sensitive and selective silver nanoparticle-based fluorescence sensor for corticosteroid determination in pharmaceutical formulations","authors":"Ghidaa G. Elawadi,&nbsp;Fawzi Elsebaei,&nbsp;Mona E. Fathy,&nbsp;Mohammed E.-S. Metwally","doi":"10.1186/s13065-025-01400-w","DOIUrl":"10.1186/s13065-025-01400-w","url":null,"abstract":"<div><p>Glucocorticoids play a crucial role in metabolic processes and have potent anti-inflammatory and immunosuppressive properties. Hence, developing a facile, sensitive, selective, and green approach to determine corticosteroids is essential. In this study, silver nanoparticles (Ag-NPs) were synthesized <i>via</i> the chemical reduction of silver nitrate using sodium borohydride in distilled water without using non-environmentally friendly organic stabilizers. The synthesized Ag-NPs exhibited high stability, as evidenced by a zeta potential measuring − 36.8 mV. Also, the average particle size was determined to be 8 ± 2 nm. These Ag-NPs were then employed as a nano fluorescence probe to establish a fluorometric assay for determining prednisolone sodium phosphate (PDN) and dexamethasone sodium phosphate (DXZ). Reduction in fluorescence intensity of Ag-NPs observed at 484 nm following excitation at 242 nm exhibited quantitative quenching upon the incremental addition of the investigated drugs, with limits of detection of 0.178 µg/mL and 0.145 µg/mL for PDN and DXZ, respectively. The quenching mechanisms were examined and explained using the Stern-Volmer and Inner Filter Effect methods. The method’s selectivity was also assessed by testing other corticosteroids. The proposed method is suitable for drug testing in pharmaceutical products and quality control labs. It follows ICH guidelines and has been confirmed to be safe and eco-friendly.</p></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01400-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404129","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 stability-illustrating HPLC-DAD method for assessment of two veterinary anti-parasitic drugs: appraisal of the method’s greenness and blueness","authors":"Mohamed A. Elsayed,&nbsp;Faisal K. Algethami,&nbsp;Abdullah N. Alotaibi,&nbsp;Huda Salem AlSalem,&nbsp;Lobna Mohammed Abd Elhalim,&nbsp;Mohammed Gamal","doi":"10.1186/s13065-025-01401-9","DOIUrl":"10.1186/s13065-025-01401-9","url":null,"abstract":"<div><p>This paper represents an effective and reliable high-performance liquid chromatography-diode array detector (HPLC-DAD) method for the regular assay of Clorsulon (CLR) and Moxidectin (MOX) anti-parasitic drugs in injection solution and pure powder without derivatization processes. The mobile phase was composed of acetonitrile: methanol: water: acetic acid (56.0: 36.0: 7.5: 0.5 by volume). Besides, a Supelcosil C18 (4.60 mm ×15.0 cm, 5.0 μm) column was selected for completing the separation and quantitation of the two aforementioned veterinary drugs at a wavelength of 254 nm. The flow rate was set at 2.0 mL min⁻¹ at the isocratic approach. We have conducted the degradation experiments using the HPLC-DAD instrument, adhering to the guidelines of the International Conference of Harmonization (ICH), subjecting CLR and MOX to light, heat, basic, acidic, and oxidative stressful conditions to figure out the ideal storage conditions and the possible medications that can be co-administered with them. CLR and MOX were quantified linearly from 400.0 to 1200.0 and from 40.0 to 120.0 µg mL⁻¹, respectively. The maximum recorded degradation results were in acidic, basic, and oxidative conditions. Therefore, strong basic or acidic medications and oxidants shouldn’t be combined with CLR and MOX in a co-formulated medication. Greenness, carbon footprint, and blueness assessments for the novel method were conducted to verify the sustainability and functionality. The thirteen subdivisions in the GAPI pictogram, which were categorized as either green or yellow, refer to moderate green aspects. The final AGREE score of 0.56 and the majority of its subdivisions, ranging from dark green to yellow, indicated a relatively moderate level of greenness. This was primarily due to the significant acetonitrile content (56%) in the mobile phase. Using the HEXAGON method, the ultimate score is 0 out of 5 since the total calculated carbon footprint is less than 0.10. An eco-friendly method is one with a reduced carbon footprint score. The innovative HPLC method’s functioning and utility are indicated via its overall BAGI score of 80.0. Generally, the outcomes of the AGREE and GAPI pictograms indicate that the HPLC-DAD has a greenness feature, despite its moderate sensitivity.</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":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01401-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396555","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":"Ecofriendly and smart spectrophotometric approaches for synchronized analysis of two antipsychotic drugs, fluoxetine and olanzapine: application to combined tablet dosages with assessment of method greenness","authors":"Sayed M Derayea,&nbsp;Huda Madian,&nbsp;Ebtihal Samir,&nbsp;Khaled M. Badr-eldin","doi":"10.1186/s13065-025-01398-1","DOIUrl":"10.1186/s13065-025-01398-1","url":null,"abstract":"<div><p>The present study was dedicated for solving the challenge of the overlapped spectra of olanzapine (OLZ) and fluoxetine (FLX) for their concurrent, accurate and precise determination without prior physical separation. The developed methods had to venture away from those that depend on chromatography, because of their negative effects on the environment due to using hazardous organic solvents as well as their high cost. The suggested methods were based on spectrophotometry combined with simple mathematical treatments of the spectra. These approaches are simple, rapid, inexpensive and reliable options for the effective assay of FLX and OLZ in pharmaceutical dosage forms. Ratio subtraction method was devoted for estimation of both drugs, while dual wavelength method and absorptivity factor method could be utilized in the estimation of FLX and OLZ, respectively. All the suggested methods were efficiently applied for the determination of the studied drugs in laboratory prepared mixtures and their pharmaceutical formulations. The environmental safety of the involved procedures was assessed by applying the Eco Score scale and complex modified GAPI methods. The methods were proved to be highly safe since no large volume of solvents were used, and no derivatizing reagent or drastic experimental conditions were involved. In addition, the procedures consume little energy and produce a small amount of waste. In conclusion, for FLX determination, the use of dual wavelength method is preferable because it needs very low mathematical treatment than the ratio subtraction method. However, for OLZ, the ratio subtraction method has higher sensitivity than absorptivity factor method although the latter is simpler.</p></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01398-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404091","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":"Ecofriendly colorimetric set-up coupled with mathematical filtration strategy for simultaneous determination of ipratropium and fenoterol in their novel anti-asthmatic metered dose inhaler","authors":"Salma N. Ali,&nbsp;Hoda M. Marzouk,&nbsp;Ahmed S. Fayed,&nbsp;Samah S. Saad","doi":"10.1186/s13065-025-01397-2","DOIUrl":"10.1186/s13065-025-01397-2","url":null,"abstract":"<div><p>Ipratropium bromide (IPR) and fenoterol hydrobromide (FEN) are well-known medications for treating asthma and chronic obstructive pulmonary disease (COPD). A simple, feasible, efficient, and cost-effective colorimetric assay has been established for determination of the newly introduced co-formulated metered dose inhaler (Atrovent^® comp HFA). The developed method is based on the properly optimized reaction of drugs under study with the charge transfer reagent 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), resulting in orange-colored complexes measured at 464.3 and 514.0 nm for IPR and FEN, respectively. Smoothly applicable and easily manipulated resolution method, Vierordt’s method, based on straightforward mathematical equations that do not need complicated software was implemented for the simultaneous determination of IPR and FEN. The proposed methodology can be applied in routine analysis enabling fast and economical determination of the combined dosage form without the need for previous separation steps. The validity of the proposed colorimetric method was thoroughly assured as per ICH guidelines with acceptable accuracy and precision. The linearity ranges for IPR and FEN were 5.0–55.0 µg/mL and 10.0–40.0 µg/mL, respectively. Using cutting-edge software metric tools, namely the analytical greenness (AGREE), and complementary green analytical procedure index (ComplexGAPI), the greenness profile of the suggested method was clearly evaluated. The method also conformed well to the recently published blueness (BAGI tool) and whiteness (RGB12 tool) concepts.</p></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01397-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143361723","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":"Application of spectrophotometry in novel simultaneous dissolution profiling of a single pill triple therapy of amlodipine, perindopril and indapamide; whiteness evaluation","authors":"Aya T. Soudi","doi":"10.1186/s13065-025-01396-3","DOIUrl":"10.1186/s13065-025-01396-3","url":null,"abstract":"<div><p>Simple, diverse univariate spectrophotometric methods were developed and validated for the determination of amlodipine besylate (AM), perindopril arginine (PE), and indapamide (ID). The first method involved direct measurement of AM absorbance at 365 nm within a concentration range of 2.00–40.00 µg/mL, where PE and ID exhibited no spectral interference. To eliminate the contribution of AM from the ternary mixture, its spectrum was divided by a reference spectrum of AM (12 µg/mL), followed by mathematical subtraction of the resulting constant. The spectrum was then multiplied by the AM divisor to yield a corrected spectrum of the PE and ID binary mixture, allowing their quantification. Various approaches were used to quantify both drugs, including measurement of their second (2DD) and first derivative (1DD) spectra at 231.30 nm and 251.00 nm, respectively. Additionally, the ratio difference (RD) technique and dual wavelength (DW) method were employed. The concentration ranges for PE and ID were 5.00–100.00 µg/mL and 1.00–20.00 µg/mL, respectively. Among these methods, the DW technique was the simplest, so it was chosen for dissolution monitoring of PE and ID. These methods were successfully applied to determine AM, PE, and ID in bulk powder, as well as in Triplixam^® tablets, without interference from excipients and in different used dissolution media. The whiteness of the method was evaluated, demonstrating its excellent environmental, analytical and practical efficiency.</p></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01396-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143361762","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":"Cobalt titanate nanocatalyst for enhanced photodegradation of atrazine: kinetics, degradation efficiency, and mechanistic analysis","authors":"Jeremiah Suleiman Nuhu,&nbsp;Femi Emmanuel Awe,&nbsp;Rajni Garg,&nbsp;Rishav Garg,&nbsp;Nnabuk Okon Eddy,&nbsp;Hazratullah Paktin","doi":"10.1186/s13065-025-01394-5","DOIUrl":"10.1186/s13065-025-01394-5","url":null,"abstract":"<div><p>In this study, cobalt titanate nanoparticles (CoTiO₃ NPs) were synthesized and applied as a photocatalyst to degrade atrazine. Scanning electron microscopic (SEM) analysis showed irregularly shaped particles prone to agglomeration, while X-ray diffraction (XRD) confirmed the formation of a rhombohedral CoTiO₃ phase with a crystallite size of 3.76 nm. Raman spectroscopic analysis showed vibrations typical for Ti–O and Co–O bonds and confirmed a well-defined cobalt titanate structure. Thermogravimetric analysis (TGA) showed that the nanoparticles remained stable up to 800 °C. The photocatalytic activity of CoTiO₃ NPs was tested under sunlight irradiation and the results obtained demonstrated excellent efficiency compared to the photolysis reaction. The efficiency was influenced by concentration (20–50 ppm), catalyst dosage (0.5–2.0 mg/L), pH (4.21–10.22), and irradiation time (0–120 min). The synthesized nanoparticles exhibited a surface area of 32.5 m²/g (DFT) and 828.03 m⁻¹ (BET), a pore volume of 0.03925 m³/g, and a bandgap energy of 2.66 eV. Kinetic studies demonstrated that the degradation followed the Langmuir–Hinshelwood model, with the photocatalytic reaction being the rate-determining step. Adsorption rate constants were found to range from 0.03828 to 0.166528 min⁻¹, while photocatalytic rate constants ranged from 0.373692 to 0.977135 min⁻¹. The CoTiO₃ NPs also showed excellent recyclability, maintaining high degradation efficiency after five cycles. Scavenger experiments confirmed that hydroxyl radicals (HO•) are responsible for atrazine degradation while GCMS analysis confirmed the complete mineralization of atrazine with carbon dioxide (CO₂) and water (H₂O) as the final degradation products.</p></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01394-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143361765","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":"Molecular imprinted polymer-based potentiometric approach for the determination of carvedilol and ivabradine hydrochloride in dosage form, spiked human plasma and in presence of their oxidative degradates","authors":"Nermine V. Fares,&nbsp;Haitham A. El Fiky,&nbsp;Dina A. Ahmed,&nbsp;Maha F. Abd El Ghany,&nbsp;Amr M. Badawey,&nbsp;Mahmoud A. Tantawy","doi":"10.1186/s13065-025-01392-7","DOIUrl":"10.1186/s13065-025-01392-7","url":null,"abstract":"<div><p>Carivalan^® pharmaceutical formulation, which includes carvedilol and ivabradine hydrochloride, is commonly prescribed for alleviating pain associated with angina. Solid contact ion-selective electrodes with wide range of applications have been developed for analysis of these two active ingredients. Those types of electrodes have common drawbacks. Aside from development of aqueous layer, the incorporated ion exchanger in plasticized membrane is usually unable to differentiate in sensing between two similarly charged lipophilic organic ions. These flaws impeded simultaneous quantification of carvedilol and ivabradine hydrochloride in their dosage form. First, attempts were made to stabilize possible signals by synthesizing hydrophobic multiwall carbon nanotubes-based carbon paste. Precipitation polymerization was used to create molecular imprinted polymers (MIPs) for each drug. MIPs’ graved cavities serve as artificial host-tailored receptors that are able to recognize and bind to individual drugs. Carvedilol MIP-based sensor showed Nernstian slope of 55.30 mV/decade while the corresponding value for ivabradine one was 55.50 mV/decade. The respective LODs were 7.0 × 10^− 8 M and 6.0 × 10^− 7 M. Interference from excipients of pharmaceutical formulation, common plasma ions, and possible oxidation byproducts was not witnessed, permitting direct and simultaneous measurement of carvedilol and ivabradine in their tablet solution and spiked human plasma. Furthermore, the proposed technique was compared favorably with the official titrimetric and reported spectrophotometric methods for analyzing carvedilol and ivabradine, respectively.</p></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01392-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143361764","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":"Multi-stage structure-based virtual screening approach combining 3D pharmacophore, docking and molecular dynamic simulation towards the identification of potential selective PARP-1 inhibitors","authors":"Mahmoud A. El Hassab,&nbsp;Wagdy M. Eldehna,&nbsp;Ghaneya S. Hassan,&nbsp;Sahar M. Abou-Seri","doi":"10.1186/s13065-025-01389-2","DOIUrl":"10.1186/s13065-025-01389-2","url":null,"abstract":"<div><p>Presently, humanity is confronted with a range of diseases that have high death rates, especially those linked to cancerous growths. Several enzymes and proteins have been discovered as highly attractive targets for cancer treatment. The PARP family consists of 17 members and plays a crucial role in repairing DNA damage, which enables the survival of cancer cells. PARP-1 and, to a lesser extent, PARP-2 display above 90% activity in response to DNA damage, thereby distinguishing them apart from other members of the PARP family. Elevated levels of PARP-1 were observed in many types of tumor cells, such as breast, lung, ovarian, prostate, and melanomas. In an attempt to provide a future guide for developing selective inhibitors for PARP-1 over PARP-2 to minimize the resulting side effects from PARP-2 inhibitors, we constructed a structure-based virtual screening approach (SBVS). Firstly. A 3D pharmacophore was constructed based on the interaction of the selective inhibitor compound <b>IV</b>. After that, a database of nearly 450,000 phthalimide-containing inhibitors was screened through the validated pharmacophore, and 165 compounds were retrieved. The retrieved compounds were docked into the active site of PARP-1 where only 5 compounds <b>MWGS-1-5</b> achieved a favorable docking score than the reference <b>IV</b> (-16.8 Kcal/mol). Redocking of the five compounds should have excellent selectivity for PARP-1 over PARP-2, especially compound <b>MWGS-1</b>. Further endorsement via molecular dynamics has proven higher affinity and selectivity for <b>MWGS-1</b> towards PARP-1 over PARP-2, in which PARP-1- <b>MWGS-1 and</b> PARP-1- <b>MWGS-1</b> achieved RMSD values of 1.42 and 2.8 Å, respectively.</p></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"19 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-025-01389-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073385","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}