Pub Date : 2025-02-19DOI: 10.1016/j.molstruc.2025.141795
C.B. Meenakshy , K.S. Sandhya , R. Gouri , D.K.S. Lekshmi , Ani Deepthi
Tryptanthrin incorporated 1-nitropyrrolizidines were synthesized with high regiospecificity in diastereomerically pure forms by the one-pot three component reaction of tryptanthrin, l-proline and β-nitrostyrene. The cis-relationship between the protons in carbons 1, 2 and 8 of the products 4a-p was confirmed by 1D NOE analysis and further support for the cis-cycloadduct formation, through endo attack of S-shaped ylide, was gained computationally. In silico docking studies, revealed that compounds 4j and 4k were the best candidates for anticancer screening and further in vitro analysis of these compounds against human breast cancer cell line-MCF-7 indicated mild activity with IC50 values 41.57 ± 0.41 µg/mL and 65.94 ± 0.34 µg/mL respectively. Results from ADMET-AI web server indicated the higher bioavailability value with a good BBB (Blood Brain Barrier) penetration score of 0.80 and 0.77 for 4j and 4k respectively. Also, both the compounds exhibited good human intestinal absorption (HIA) value, less carcinogenicity (0.41 and 0.42) and high excretion rate (91.55 % and 89.96 %).
{"title":"Synthesis and anticancer evaluation of tryptanthrin appended spiro1-nitropyrrolizidine derivatives by the three-component reaction of tryptanthrin, l-proline and β-nitrostyrene","authors":"C.B. Meenakshy , K.S. Sandhya , R. Gouri , D.K.S. Lekshmi , Ani Deepthi","doi":"10.1016/j.molstruc.2025.141795","DOIUrl":"10.1016/j.molstruc.2025.141795","url":null,"abstract":"<div><div>Tryptanthrin incorporated 1-nitropyrrolizidines were synthesized with high regiospecificity in diastereomerically pure forms by the one-pot three component reaction of tryptanthrin, <span>l</span>-proline and <em>β</em>-nitrostyrene. The <em>cis</em>-relationship between the protons in carbons 1, 2 and 8 of the products <strong>4a-p</strong> was confirmed by 1D NOE analysis and further support for the <em>cis</em>-cycloadduct formation, through <em>endo</em> attack of S-shaped ylide, was gained computationally. <em>In silico</em> docking studies, revealed that compounds <strong>4j</strong> and <strong>4k</strong> were the best candidates for anticancer screening and further <em>in vitro</em> analysis of these compounds against human breast cancer cell line-MCF-7 indicated mild activity with IC<sub>50</sub> values 41.57 ± 0.41 <em>µ</em>g/mL and 65.94 ± 0.34 <em>µ</em>g/mL respectively. Results from ADMET-AI web server indicated the higher bioavailability value with a good BBB (Blood Brain Barrier) penetration score of 0.80 and 0.77 for <strong>4j</strong> and <strong>4k</strong> respectively. Also, both the compounds exhibited good human intestinal absorption (HIA) value, less carcinogenicity (0.41 and 0.42) and high excretion rate (91.55 % and 89.96 %).</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1334 ","pages":"Article 141795"},"PeriodicalIF":4.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-19DOI: 10.1016/j.molstruc.2025.141766
Tejaswini P. Siddappa , Akshay Ravish , Narasimha M Beeraka , Shreeja Basappa , Kanchugarakoppa S Rangappa , Vladimir N Nikolenko , Basappa Basappa
Breast cancer is a prevalent malignancy among women, posing significant public health challenges globally. Nuclear factor kappa B (NF-κB) pathway is implicated in breast cancer development and progression. This study aims to achieve the comprehensive chemical synthesis of oxazine derivatives and evaluate their potential as anticancer agents. Additionally, it involves conducting in silico analysis to assess the interaction of these compounds with the NF-κB pathway in human breast cancer cells. Oxazine derivatives were synthesized and evaluated for their anticancer activity against MCF-7 cells by cell viability assays. To determine the mass of the synthesized molecules, mass spectrometer was used. Additionally, 1H and 13C NMR spectra were acquired using mass spectometry and NMR study. In silico analysis was conducted to assess the binding affinity of these compounds towards human NF-κB protein (1IKN). Among the synthesized compounds, oxazine derivative 6a demonstrated the highest potency with an IC50 of 13.22 µM against MCF-7 cells. In silico analysis revealed that all synthesized compounds exhibited favorable binding energies towards the human NF-κB protein (1IKN). Oxazine derivatives, exemplified by compound 6a, show significant promise as effective agents against breast cancer cells, notably through NF-κB inhibition. The integration of computational methods in drug discovery describes their utility in optimizing compound design and understanding molecular interactions.
{"title":"Novel oxadiazolyl-thio and triazolyl-thio-heterocylces: Synthesis, characterization, and In Silico Screening for Targeting NF-κB in Breast Cancer Cells","authors":"Tejaswini P. Siddappa , Akshay Ravish , Narasimha M Beeraka , Shreeja Basappa , Kanchugarakoppa S Rangappa , Vladimir N Nikolenko , Basappa Basappa","doi":"10.1016/j.molstruc.2025.141766","DOIUrl":"10.1016/j.molstruc.2025.141766","url":null,"abstract":"<div><div>Breast cancer is a prevalent malignancy among women, posing significant public health challenges globally. Nuclear factor kappa B (NF-κB) pathway is implicated in breast cancer development and progression. This study aims to achieve the comprehensive chemical synthesis of oxazine derivatives and evaluate their potential as anticancer agents. Additionally, it involves conducting in silico analysis to assess the interaction of these compounds with the NF-κB pathway in human breast cancer cells. Oxazine derivatives were synthesized and evaluated for their anticancer activity against MCF-7 cells by cell viability assays. To determine the mass of the synthesized molecules, mass spectrometer was used. Additionally, <sup>1</sup>H and <sup>13</sup>C NMR spectra were acquired using mass spectometry and NMR study. In silico analysis was conducted to assess the binding affinity of these compounds towards human NF-κB protein (1IKN). Among the synthesized compounds, oxazine derivative <strong>6a</strong> demonstrated the highest potency with an IC<sub>50</sub> of 13.22 µM against MCF-7 cells. In silico analysis revealed that all synthesized compounds exhibited favorable binding energies towards the human NF-κB protein (1IKN). Oxazine derivatives, exemplified by compound <strong>6a</strong>, show significant promise as effective agents against breast cancer cells, notably through NF-κB inhibition. The integration of computational methods in drug discovery describes their utility in optimizing compound design and understanding molecular interactions.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1334 ","pages":"Article 141766"},"PeriodicalIF":4.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-19DOI: 10.1016/j.molstruc.2025.141800
Fakhreddine Ben Amara , Franciele da Silva Bruckmann , Suliman Yousef Alomar , Marcos Leandro Silva Oliveira , Luis Felipe Oliveira Silva , Guilherme Luiz Dotto , Samir Bejar , Sonia Jemli
Herein, a new superadsorbent was synthesized via a crosslinking reaction using β-cyclodextrin and coffee grounds and employed to remove two organic cationic molecules, methylene blue and crystal violet. The interactions between adsorbent-adsorbate in aqueous media were also investigated. The material was characterized by FTIR, XRD, SEM, EDX, and DSC techniques, and adsorption was investigated through the kinetic, isotherms, and thermodynamic parameters. Sips isotherm was the more suitable model for fitting the adsorption equilibrium, while the pseudo-first-order model for both dyes described the kinetic data well. The new adsorbent presented impressive adsorption capacity values, higher than 1500 mg g−1. This high adsorption capacity results from three main mechanisms: electrostatic attraction, hydrogen bonds, and hydrophobic interactions between the hydrophobic parts of dyes and the inner hydrophobic cavity of cyclodextrin. Thermodynamic parameters revealed an endothermic and spontaneous process with increased randomness in the liquid-solid interface. Overall, the adsorbent exhibited an excellent performance for dye removal and potential use in wastewater treatment plants.
{"title":"A novel superadsorbent β-cyclodextrin crosslinked coffee grounds biopolymer to remove organic molecules from water matrices","authors":"Fakhreddine Ben Amara , Franciele da Silva Bruckmann , Suliman Yousef Alomar , Marcos Leandro Silva Oliveira , Luis Felipe Oliveira Silva , Guilherme Luiz Dotto , Samir Bejar , Sonia Jemli","doi":"10.1016/j.molstruc.2025.141800","DOIUrl":"10.1016/j.molstruc.2025.141800","url":null,"abstract":"<div><div>Herein, a new superadsorbent was synthesized via a crosslinking reaction using β-cyclodextrin and coffee grounds and employed to remove two organic cationic molecules, methylene blue and crystal violet. The interactions between adsorbent-adsorbate in aqueous media were also investigated. The material was characterized by FTIR, XRD, SEM, EDX, and DSC techniques, and adsorption was investigated through the kinetic, isotherms, and thermodynamic parameters. Sips isotherm was the more suitable model for fitting the adsorption equilibrium, while the pseudo-first-order model for both dyes described the kinetic data well. The new adsorbent presented impressive adsorption capacity values, higher than 1500 mg g<sup>−1</sup>. This high adsorption capacity results from three main mechanisms: electrostatic attraction, hydrogen bonds, and hydrophobic interactions between the hydrophobic parts of dyes and the inner hydrophobic cavity of cyclodextrin. Thermodynamic parameters revealed an endothermic and spontaneous process with increased randomness in the liquid-solid interface. Overall, the adsorbent exhibited an excellent performance for dye removal and potential use in wastewater treatment plants.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1334 ","pages":"Article 141800"},"PeriodicalIF":4.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-19DOI: 10.1016/j.molstruc.2025.141798
Hayat Ullah , Fazal Rahim , Shoaib Khan , Tayyiaba Iqbal , Muhammad Bilal Khan , Rashid Iqbal , Hamid Ali , Mashooq Ahmad Bhat
A novel series of hybrid thiazole derived triazole based thiosemicarbazone derivatives (1–14) were synthesized by an efficient synthetic approach to examine their biological potential against diabetes mellitus (DM) to identify lead candidates. All these synthesized compounds exhibit excellent to moderate potency in comparison to the standard drug acarbose (IC50= 38.45± 0.80 and 11.12± 0.15 µM, respectively against α-glucosidase and α-amylase. Among these compounds, analogue 3 (IC50 = 9.40± 0.30 and 5.30± 0.20 µM) has remarkable efficacy and is recognized as a lead candidate. Binding folds of potent analogs with protein complex were assessed via in silico docking study and the results revealed spellbinding interactions. Moreover, ADMET analysis fosters the drug likeness characteristics of active analogs.
{"title":"Comparative studies determined the role of hybrid thiazole-triazole based thiosemicarbazone as anti-diabetic agent: Synthetic confirmation, Molecular docking and ADMET analysis","authors":"Hayat Ullah , Fazal Rahim , Shoaib Khan , Tayyiaba Iqbal , Muhammad Bilal Khan , Rashid Iqbal , Hamid Ali , Mashooq Ahmad Bhat","doi":"10.1016/j.molstruc.2025.141798","DOIUrl":"10.1016/j.molstruc.2025.141798","url":null,"abstract":"<div><div>A novel series of hybrid thiazole derived triazole based thiosemicarbazone derivatives (<strong>1–14</strong>) were synthesized by an efficient synthetic approach to examine their biological potential against diabetes mellitus (DM) to identify lead candidates. All these synthesized compounds exhibit excellent to moderate potency in comparison to the standard drug acarbose (IC<sub>50</sub>= <strong>38.45</strong> <strong>± 0.80</strong> and <strong>11.12</strong> <strong>± 0.15</strong> µM, respectively against α-glucosidase and α-amylase. Among these compounds, analogue <strong>3</strong> (IC<sub>50</sub> = <strong>9.40</strong> <strong>± 0.30</strong> and <strong>5.30</strong> <strong>± 0.20</strong> µM) has remarkable efficacy and is recognized as a lead candidate. Binding folds of potent analogs with protein complex were assessed via <em>in silico</em> docking study and the results revealed spellbinding interactions. Moreover, ADMET analysis fosters the drug likeness characteristics of active analogs.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1334 ","pages":"Article 141798"},"PeriodicalIF":4.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-18DOI: 10.1016/j.molstruc.2025.141779
Mostafa Ahmed , Mahmoud M. Hamed , Mostafa Sayed , Ahmed A. El-Rashedy , Adel M. Kamal El-Dean , Mohammad H.A. Hassan , Mohamed F. Mady , Mahmoud S. Tolba
Propylthiouracil (PTU) and its derivatives exhibit a wide range of biological activities, making them valuable compounds in pharmacology and medicinal chemistry. In the present work some new heterocyclic compounds (2–9) were synthesized through multi steps using propylthiouracil (PTU) 1 as starting material. The claimed chemical structures of all new synthesized compounds were elucidated by spectral analysis including FTIR, NMR and Mass spectroscopy. Furthermore, the antimicrobial activity for all synthesized compounds were investigated against different strains of bacteria and fungi. The results suggested that compounds 3, 5, 6a, 6b, 6c, 7b demonstrate positive results against the Fluconazole" as the antifungal positive control, while compounds 5, 6a 6c, 8 show positive results against Cefotaxime" as the antibacterial positive control. Moreover, molecular dynamic simulations revealed that compound 5 demonstrated significant interactions with essential residues of the binding site, resulting in a stable complex throughout the entire simulation run.
{"title":"Synthesis, antimicrobial activity, molecular docking and molecular dynamics studies of novel bioactive compounds derived from propylthiouracil","authors":"Mostafa Ahmed , Mahmoud M. Hamed , Mostafa Sayed , Ahmed A. El-Rashedy , Adel M. Kamal El-Dean , Mohammad H.A. Hassan , Mohamed F. Mady , Mahmoud S. Tolba","doi":"10.1016/j.molstruc.2025.141779","DOIUrl":"10.1016/j.molstruc.2025.141779","url":null,"abstract":"<div><div>Propylthiouracil (PTU) and its derivatives exhibit a wide range of biological activities, making them valuable compounds in pharmacology and medicinal chemistry. In the present work some new heterocyclic compounds (<strong>2</strong>–<strong>9</strong>) were synthesized through multi steps using propylthiouracil (PTU) <strong>1</strong> as starting material. The claimed chemical structures of all new synthesized compounds were elucidated by spectral analysis including FTIR, NMR and Mass spectroscopy. Furthermore, the antimicrobial activity for all synthesized compounds were investigated against different strains of bacteria and fungi. The results suggested that compounds <strong>3, 5, 6a, 6b, 6c, 7b</strong> demonstrate positive results against the Fluconazole\" as the antifungal positive control, while compounds <strong>5, 6a 6c, 8</strong> show positive results against Cefotaxime\" as the antibacterial positive control. Moreover, molecular dynamic simulations revealed that compound <strong>5</strong> demonstrated significant interactions with essential residues of the binding site, resulting in a stable complex throughout the entire simulation run.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1333 ","pages":"Article 141779"},"PeriodicalIF":4.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-18DOI: 10.1016/j.molstruc.2025.141791
Surya Uthrapathy , Balasankar Thirunavukkarasu , Tanzeer Ahmad Dar , Udhayanithi Muthusamy Karunanithi
Phthalazine ring bearing piperidin-4-one based hydrazone derivatives 2(a-e) were synthesized by incorporating a biologically active phthalazine ring into the piperidin-4-one moeity through hydrazone formation. The structure of the compounds 2(a-e) were identified by FT-IR, 1H NMR, 13C NMR, HSQC and HRMS-ESI spectral studies which furnished the clear evidence of the expected structures. From the NMR analysis, it was evident that the piperidin-4-one ring possesses a chair conformation, and all the compounds display an (E)-configuration around the C=N bond. DFT calculations for compound 2b, using a 6-311++G(d,p) basis set, provided insights into the electronic properties of the compounds. Hydrazone ligands were docked with the bacterial protein (PDB ID: 4HLC) through Autodock 4.0. All the ligands demonstrate significant binding energy values between -6.15 and -7.79 kcal/mol. ADME studies reveals the favorable pharmacokinetic profiles of the compounds. The antibacterial activity of the synthesized compounds 2(a-e) was evaluated using the agar well diffusion method, where the inhibitory zone was measured to assess their antibacterial properties. Compounds with bromo and methyl substitutions (2c and 2d) show outstanding inhibition against the pathogens used.
{"title":"Phthalazine ring incorporated 3-methyl-2,6-diarylpiperidin-4-one based hybrids: Synthesis, Spectral characterization, DFT studies, Molecular docking, In silico ADME predictions and Antibacterial activity","authors":"Surya Uthrapathy , Balasankar Thirunavukkarasu , Tanzeer Ahmad Dar , Udhayanithi Muthusamy Karunanithi","doi":"10.1016/j.molstruc.2025.141791","DOIUrl":"10.1016/j.molstruc.2025.141791","url":null,"abstract":"<div><div>Phthalazine ring bearing piperidin-4-one based hydrazone derivatives <strong>2(a-e)</strong> were synthesized by incorporating a biologically active phthalazine ring into the piperidin-4-one moeity through hydrazone formation. The structure of the compounds <strong>2(a-e)</strong> were identified by FT-IR, <sup>1</sup>H NMR, <sup>13</sup>C NMR, HSQC and HRMS-ESI spectral studies which furnished the clear evidence of the expected structures. From the NMR analysis, it was evident that the piperidin-4-one ring possesses a chair conformation, and all the compounds display an <em>(E)-</em>configuration around the C=N bond. DFT calculations for compound <strong>2b</strong>, using a 6-311++G(d,p) basis set, provided insights into the electronic properties of the compounds. Hydrazone ligands were docked with the bacterial protein (PDB ID: <span><span><em>4HLC</em></span><svg><path></path></svg></span><em>)</em> through Autodock 4.0. All the ligands demonstrate significant binding energy values between -6.15 and -7.79 kcal/mol. ADME studies reveals the favorable pharmacokinetic profiles of the compounds. The antibacterial activity of the synthesized compounds <strong>2(a-e)</strong> was evaluated using the agar well diffusion method, where the inhibitory zone was measured to assess their antibacterial properties. Compounds with bromo and methyl substitutions <strong>(2c and 2d)</strong> show outstanding inhibition against the pathogens used.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1334 ","pages":"Article 141791"},"PeriodicalIF":4.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143507954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-18DOI: 10.1016/j.molstruc.2025.141790
Josias S. Rocha , George B.S. Pereira , Marcos V. Palmeira-Mello , Willyan F. Oliveira , Jocely L. Dutra , Tamara Teixeira , Nádija N.P. da Silva , Gabriela P. Oliveira , Paulo C. Gomes-Junior , Anna C.S.J. Passaes , João H. Araujo-Neto , Alzir A. Batista , Javier Ellena , José D.L. Dutra , Renan L. Farias , Fillipe V. Rocha
In this study, two complexes based on Europium [Eu(LAW)3(H2O)3] (1) and Terbium [Tb(LAW)3(H2O)3] (2), each containing the lawsone ligand, were synthesized and comprehensively characterized using Infrared and UV-Visible spectroscopies, Cyclic Voltammetry, Conductivity, and Magnetic Susceptibility measurements. Crystal structure information was determined via X-ray diffraction (XRD), and elemental analysis confirmed the compounds’ purity. Experimental and theoretical UV-Vis data were compared through TD-DFT calculations, providing insights into the low luminescence of both Eu(III) and Tb(III) complexes, with excited states calculated both with and without solvent effects. DNA-binding experiments with ct-DNA were conducted using viscosity measurements, UV-Vis titrations, circular dichroism, and fluorescence competition assays to explore the complexes' primary interactions with the DNA target. Additionally, DNA cleavage properties were examined using pBR322 plasmid DNA with agarose gel electrophoresis. Although no cleavage activity was observed, DNA interaction studies suggested covalent binding, supported by viscosity and circular dichroism data. Furthermore, analyzing the docking results, both compounds demonstrated stable conformations within the Sudlow I site also the lawsone-based compounds demonstrated an ability to bind to human serum albumin (HSA) with binding constants (Kb) in the range of 105-106 and showed Topoisomerase IIα inhibition at 50 µM. Both compounds remained stable for up to 48 hours.
{"title":"Synthesis, characterization of europium(III) and terbium(III) complexes containing lawsone ligand and their interaction with DNA, HSA, and topoisomerases","authors":"Josias S. Rocha , George B.S. Pereira , Marcos V. Palmeira-Mello , Willyan F. Oliveira , Jocely L. Dutra , Tamara Teixeira , Nádija N.P. da Silva , Gabriela P. Oliveira , Paulo C. Gomes-Junior , Anna C.S.J. Passaes , João H. Araujo-Neto , Alzir A. Batista , Javier Ellena , José D.L. Dutra , Renan L. Farias , Fillipe V. Rocha","doi":"10.1016/j.molstruc.2025.141790","DOIUrl":"10.1016/j.molstruc.2025.141790","url":null,"abstract":"<div><div>In this study, two complexes based on Europium [Eu(LAW)<sub>3</sub>(H<sub>2</sub>O)<sub>3</sub>] <strong>(1)</strong> and Terbium [Tb(LAW)<sub>3</sub>(H<sub>2</sub>O)<sub>3</sub>] <strong>(2)</strong>, each containing the lawsone ligand, were synthesized and comprehensively characterized using Infrared and UV-Visible spectroscopies, Cyclic Voltammetry, Conductivity, and Magnetic Susceptibility measurements. Crystal structure information was determined via X-ray diffraction (XRD), and elemental analysis confirmed the compounds’ purity. Experimental and theoretical UV-Vis data were compared through TD-DFT calculations, providing insights into the low luminescence of both Eu(III) and Tb(III) complexes, with excited states calculated both with and without solvent effects. DNA-binding experiments with ct-DNA were conducted using viscosity measurements, UV-Vis titrations, circular dichroism, and fluorescence competition assays to explore the complexes' primary interactions with the DNA target. Additionally, DNA cleavage properties were examined using pBR322 plasmid DNA with agarose gel electrophoresis. Although no cleavage activity was observed, DNA interaction studies suggested covalent binding, supported by viscosity and circular dichroism data. Furthermore, analyzing the docking results, both compounds demonstrated stable conformations within the Sudlow I site also the lawsone-based compounds demonstrated an ability to bind to human serum albumin (HSA) with binding constants (K<sub>b</sub>) in the range of 10<sup>5</sup>-10<sup>6</sup> and showed Topoisomerase IIα inhibition at 50 µM. Both compounds remained stable for up to 48 hours.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1333 ","pages":"Article 141790"},"PeriodicalIF":4.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-18DOI: 10.1016/j.molstruc.2025.141796
Muhammad Ibrahim , Mumtaz Ali , Sobia Ahsan Halim , Sajid Ali , Abdul Latif , Manzoor Ahmad , Muhammad Zubair , Satya Kumar Avula , Magda H. Abdellattif , Ajmal Khan , Ahmed Al-Harrasi
The present research work is employed with the synthesis of 4,4ꞌ-sulfinyldiphenol-linked hydrazones, their in-vitro evaluation as cholinesterase inhibitors, and their molecular docking analysis. A total of 29 new bis(acylhydrazones) scaffolds (4–32) were recently synthesized in moderate to high yields utilizing 4,4-dithiophenol to serve as precursor. All the synthesized compounds were characterized through spectroscopic techniques such as 1H NMR, 13C NMR and HRMS-ESI+. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were used as biological targets in order to conduct in-vitro anticholinesterase efficacy using these substances. Among all, compounds 11 (IC50 = 66.3 ± 1.3 µM) and 13 (IC50 = 62.3 ± 0.6 µM) showed the most significant AChE inhibitory potential as compared to the standard inhibitor, galantamine (IC50 = 69.7 ± 0.18 µM). While compound 9 showed excellent inhibition of BChE (IC50 = 53.9 ± 2.6 µM), and compounds 14, 25 and 32 exhibited the significant dual inhibition of AChE and BChE. The molecular docking of most active compounds (13 for AChE and 14 for BChE) indicates excellent binding potential of those inhibitors with their respective targets. The study reflect that those molecules can be considered as drug-like candidate upon further optimization.
{"title":"Synthesis, in-vitro evaluation and in-silico analysis of new anticholinesterase inhibitors based on sulfinylbis(acylhydrazones) scaffolds","authors":"Muhammad Ibrahim , Mumtaz Ali , Sobia Ahsan Halim , Sajid Ali , Abdul Latif , Manzoor Ahmad , Muhammad Zubair , Satya Kumar Avula , Magda H. Abdellattif , Ajmal Khan , Ahmed Al-Harrasi","doi":"10.1016/j.molstruc.2025.141796","DOIUrl":"10.1016/j.molstruc.2025.141796","url":null,"abstract":"<div><div>The present research work is employed with the synthesis of 4,4ꞌ-sulfinyldiphenol-linked hydrazones, their <em>in-vitro</em> evaluation as cholinesterase inhibitors, and their molecular docking analysis. A total of 29 new bis(acylhydrazones) scaffolds (4–32) were recently synthesized in moderate to high yields utilizing 4,4-dithiophenol to serve as precursor. All the synthesized compounds were characterized through spectroscopic techniques such as <sup>1</sup>H NMR, <sup>13</sup>C NMR and HRMS-ESI<sup>+</sup>. <em>Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were used as biological targets in order to conduct in-vitro anticholinesterase efficacy using these substances.</em> Among all, compounds <strong>11</strong> (IC<sub>50</sub> = 66.3 ± 1.3 µM) and <strong>13</strong> (IC<sub>50</sub> = 62.3 ± 0.6 µM) showed the most significant AChE inhibitory potential as compared to the standard inhibitor, galantamine (IC<sub>50</sub> = 69.7 ± 0.18 µM). While compound <strong>9</strong> showed excellent inhibition of BChE (IC<sub>50</sub> = 53.9 ± 2.6 µM), and compounds <strong>14, 25</strong> and <strong>32</strong> exhibited the significant dual inhibition of AChE and BChE. The molecular docking of most active compounds (<strong>13</strong> for AChE and <strong>14</strong> for BChE) indicates excellent binding potential of those inhibitors with their respective targets. The study reflect that those molecules can be considered as drug-like candidate upon further optimization.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1334 ","pages":"Article 141796"},"PeriodicalIF":4.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-18DOI: 10.1016/j.molstruc.2025.141789
Ali H. Abdelrahman , Mohammad E. Azab , Mohamed A. Hegazy , Ahmed Labena , Abdullah Y.A. Alzahrani , Sayed K. Ramadan
Anticancer drug acquiring usually discloses with an in vitro testing in cell panels to certainly detect the lead compounds. EGFR is a tyrosine kinase cell surface receptor that plays a key function in signal transduction processes and is observed on most cell surfaces. One of the promising frameworks in drug detection is pyrimidine and its fused heteroannulated bicyclic derivatives which exhibited promising anticancer activity. The prepared triazolopyrimidine and thiazolopyrimidine derivatives were proposed to fit into the ATP binding site of EGFR protein. The in vitro antiproliferative screening against MCF7 and HCT116 cancer cell panels disclosed the most influence of triazolopyrimidine 3, thiazolopyrimidine 9, and pyrimidinethione 1 compared to the reference drug, roscovitine (imidazopyrimidine hybrid). The inhibitory action of the most promising compounds was explored versus EGFR enzyme, which displayed the highest efficacy of triazolopyrimidine 3 compared to the standard drug (erlotinib). The structure-activity relationship (SAR) probe demonstrated that specific structural modifications had a significant impact on the antiproliferative action. In silico molecular docking was performed on these promising compounds versus EGFR enzyme (breast cancer protease, PDB ID: 3W32) to show the enzyme-inhibitor interactions, which uncovered the superlative binding interactions of triazolopyrimidine 3 with key nucleobases and amino acids of EGFR kinase. Among DFT calculations, ELUMO of compounds 3< 1< 9, which enriched its binding affinity of with nucleophilic receptor's active pockets. Regarding ADME simulation, they had gastrointestinal tract (GIT) absorption, good bioavailability score, and worthy lead-likeness. This work may contribute to developing new effective EGFR inhibitor.
{"title":"Synthesis, computational analysis, and exploring antiproliferative activity of triazolo- and thiazolo-pyrimidine derivatives as potential EGFR inhibitors","authors":"Ali H. Abdelrahman , Mohammad E. Azab , Mohamed A. Hegazy , Ahmed Labena , Abdullah Y.A. Alzahrani , Sayed K. Ramadan","doi":"10.1016/j.molstruc.2025.141789","DOIUrl":"10.1016/j.molstruc.2025.141789","url":null,"abstract":"<div><div>Anticancer drug acquiring usually discloses with an in vitro testing in cell panels to certainly detect the lead compounds. EGFR is a tyrosine kinase cell surface receptor that plays a key function in signal transduction processes and is observed on most cell surfaces. One of the promising frameworks in drug detection is pyrimidine and its fused heteroannulated bicyclic derivatives which exhibited promising anticancer activity. The prepared triazolopyrimidine and thiazolopyrimidine derivatives were proposed to fit into the ATP binding site of EGFR protein. The <em>in vitro</em> antiproliferative screening against MCF7 and HCT116 cancer cell panels disclosed the most influence of triazolopyrimidine <strong>3</strong>, thiazolopyrimidine <strong>9</strong>, and pyrimidinethione <strong>1</strong> compared to the reference drug, roscovitine (imidazopyrimidine hybrid). The inhibitory action of the most promising compounds was explored versus EGFR enzyme, which displayed the highest efficacy of triazolopyrimidine <strong>3</strong> compared to the standard drug (erlotinib). The structure-activity relationship (SAR) probe demonstrated that specific structural modifications had a significant impact on the antiproliferative action. <em>In silico</em> molecular docking was performed on these promising compounds versus EGFR enzyme (breast cancer protease, PDB ID: <span><span>3W32</span><svg><path></path></svg></span>) to show the enzyme-inhibitor interactions, which uncovered the superlative binding interactions of triazolopyrimidine <strong>3</strong> with key nucleobases and amino acids of EGFR kinase. Among DFT calculations, E<sub>LUMO</sub> of compounds <strong>3</strong> <strong>< 1</strong> <strong>< 9</strong>, which enriched its binding affinity of with nucleophilic receptor's active pockets. Regarding ADME simulation, they had gastrointestinal tract (GIT) absorption, good bioavailability score, and worthy lead-likeness. This work may contribute to developing new effective EGFR inhibitor.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1333 ","pages":"Article 141789"},"PeriodicalIF":4.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-18DOI: 10.1016/j.molstruc.2025.141768
Atieh Rezvanian , Elham Mardi , Pezhman Shiri
Sequential transformations of three or more substrates in multicomponent reactions are known to yield architecturally intricate products. A vast majority of substrate components are transformed into the intended products with minimal generation of byproducts. The efficiency and variety of these reactions have led to their prominence in synthetic organic chemistry. Recently, the importance of enantioselective multicomponent processes has grown, especially in the domain of pharmaceutical and biological molecule synthesis, due to the unique biological properties displayed by enantiomers and diastereomers. The objective of the present review article is to provide an overview of the progress made in the enantioselective synthesis of compounds using multicomponent reactions, focusing on recent publications.
{"title":"An overview of recent advances in enantioselective multicomponent reactions","authors":"Atieh Rezvanian , Elham Mardi , Pezhman Shiri","doi":"10.1016/j.molstruc.2025.141768","DOIUrl":"10.1016/j.molstruc.2025.141768","url":null,"abstract":"<div><div>Sequential transformations of three or more substrates in multicomponent reactions are known to yield architecturally intricate products. A vast majority of substrate components are transformed into the intended products with minimal generation of byproducts. The efficiency and variety of these reactions have led to their prominence in synthetic organic chemistry. Recently, the importance of enantioselective multicomponent processes has grown, especially in the domain of pharmaceutical and biological molecule synthesis, due to the unique biological properties displayed by enantiomers and diastereomers. The objective of the present review article is to provide an overview of the progress made in the enantioselective synthesis of compounds using multicomponent reactions, focusing on recent publications.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1334 ","pages":"Article 141768"},"PeriodicalIF":4.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143507953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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