Pub Date : 2024-11-03DOI: 10.1016/j.molstruc.2024.140592
Xiangrong Li , Jingjing Zhao , Zhizhi Song , Li Shi
The interaction mechanism of trypsin/pepsin-doxycycline hyclate-quercetin ternary system was investigated by the molecular docking, molecular dynamics simulation and multiple spectroscopic methods. The results show that when doxycycline hyclate and quercetin are bound with trypsin/pepsin in sequence to form the ternary system, the different sequence of doxycycline hyclate/quercetin binding has different effects on the binding affinity of the two drugs and trypsin/pepsin. However, the binding site of the two drugs on trypsin/pepsin is basically the same as that of the corresponding binary system, except for pepsin-doxycycline hyclate (first)-quercetin ternary system. For the trypsin-quercetin (first)-doxycycline hyclate ternary system, the activity of trypsin is inhibited due to the presence of quercetin. The doxycycline hyclate that binding first even affects the binding site of quercetin and the inhibition of pepsin activity. When doxycycline hyclate and quercetin bind with trypsin/pepsin at the same time, the binding site of doxycycline hyclate and quercetin on trypsin/pepsin is completely different from their corresponding binary system. The values of binding constant of 104 L mol−1 indicate that the binding affinity are all moderate. In ternary system, the free concentration of doxycycline hyclate and quercetin in trypsin/pepsin is higher than that in binary system. Hydrophobic interactions, electrostatic forces and hydrogen bonds are the main non-covalent forces. The extent of unfolding of trypsin/pepsin peptide backbone in ternary system is greater than that in binary system. The effects of binary and ternary systems on the secondary structure of trypsin/pepsin are not significantly different, and both results in the reduction of trypsin/pepsin β-sheet.
通过分子对接、分子动力学模拟和多种光谱方法研究了胰蛋白酶/胃蛋白酶-土霉素强力霉素-槲皮素三元体系的相互作用机理。结果表明，当强力霉素和槲皮素依次与胰蛋白酶/胃蛋白酶结合形成三元体系时，强力霉素/槲皮素结合的不同顺序对两种药物与胰蛋白酶/胃蛋白酶的结合亲和力有不同的影响。但是，除了胃蛋白酶-强力霉素-槲皮素三元体系外，两种药物与胰蛋白酶/胃蛋白酶的结合位点与相应的二元体系基本相同。在胰蛋白酶-槲皮素（原）-环酸多西环素三元体系中，由于槲皮素的存在，胰蛋白酶的活性受到抑制。首先结合的环酸多西环素甚至会影响槲皮素的结合位点和对胃蛋白酶活性的抑制。当多西环素和槲皮素同时与胰蛋白酶/胃蛋白酶结合时，多西环素和槲皮素在胰蛋白酶/胃蛋白酶上的结合位点与相应的二元体系完全不同。其结合常数为 104 L mol-1，表明其结合亲和力均为中等。在三元体系中，土霉素和槲皮素在胰蛋白酶/胃蛋白酶中的游离浓度高于二元体系。疏水作用力、静电力和氢键是主要的非共价作用力。三元体系中胰蛋白酶/胃蛋白酶肽骨的展开程度大于二元体系。二元和三元体系对胰蛋白酶/胃蛋白酶二级结构的影响没有显著差异，都会导致胰蛋白酶/胃蛋白酶β片的减少。
{"title":"Study on the interaction mechanism of trypsin/pepsin-doxycycline hyclate-quercetin ternary system","authors":"Xiangrong Li , Jingjing Zhao , Zhizhi Song , Li Shi","doi":"10.1016/j.molstruc.2024.140592","DOIUrl":"10.1016/j.molstruc.2024.140592","url":null,"abstract":"<div><div>The interaction mechanism of trypsin/pepsin-doxycycline hyclate-quercetin ternary system was investigated by the molecular docking, molecular dynamics simulation and multiple spectroscopic methods. The results show that when doxycycline hyclate and quercetin are bound with trypsin/pepsin in sequence to form the ternary system, the different sequence of doxycycline hyclate/quercetin binding has different effects on the binding affinity of the two drugs and trypsin/pepsin. However, the binding site of the two drugs on trypsin/pepsin is basically the same as that of the corresponding binary system, except for pepsin-doxycycline hyclate (first)-quercetin ternary system. For the trypsin-quercetin (first)-doxycycline hyclate ternary system, the activity of trypsin is inhibited due to the presence of quercetin. The doxycycline hyclate that binding first even affects the binding site of quercetin and the inhibition of pepsin activity. When doxycycline hyclate and quercetin bind with trypsin/pepsin at the same time, the binding site of doxycycline hyclate and quercetin on trypsin/pepsin is completely different from their corresponding binary system. The values of binding constant of 10<sup>4</sup> L mol<sup>−1</sup> indicate that the binding affinity are all moderate. In ternary system, the free concentration of doxycycline hyclate and quercetin in trypsin/pepsin is higher than that in binary system. Hydrophobic interactions, electrostatic forces and hydrogen bonds are the main non-covalent forces. The extent of unfolding of trypsin/pepsin peptide backbone in ternary system is greater than that in binary system. The effects of binary and ternary systems on the secondary structure of trypsin/pepsin are not significantly different, and both results in the reduction of trypsin/pepsin β-sheet.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1322 ","pages":"Article 140592"},"PeriodicalIF":4.0,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657016","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 : 2024-11-03DOI: 10.1016/j.molstruc.2024.140562
Udaya Rajesh R, Dhanaraj Sangeetha
Secondary phenolic metabolites like flavonoids, that are found in numerous plant sections and have a range of uses. Quercetin falls under the category of flavonols, belonging to the flavonoids found in various medicinal plants, some common fruits, and vegetables with various applications. However, quercetin, with its various applications, is not well established in the pharmaceutical industry since it is associated with a lot of drawbacks, like instability in the gastrointestinal tract, the first-pass effect, solubility issues, etc. Quercetin-Schiff base derivatives are essential for targeting cancer cells and enhancing biological activities due to the formation of the C=N (imine group), which plays a major role in enhancing biological activities. In this research article, quercetin Schiff base (Q1sb) was synthesised and analysed using spectroscopic techniques like 1H NMR, 13C NMR, HRMS, etc. Biological activities like anti-bacterial, antioxidant, anti-inflammatory, and cytotoxicity analyses were done on four cancer cell lines, namely A549, HeLa, HepG2, and MCF-7, and molecular docking were done on some of the common targets. The first section explains the characteristics of flavonoid, the therapeutic action and drawbacks of quercetin, and the importance of Schiff base derivatives; the second section explains the synthesis method and characterization; and the third section explains the biological applications and molecular docking studies.
{"title":"Synthesis and characterization of 2-(3,4-dihydroxyphenyl)-4-((4-hydroxyphenyl)imino)-4h-chromene-3,5,7-triol: In vitro biological evaluation and computational analysis","authors":"Udaya Rajesh R, Dhanaraj Sangeetha","doi":"10.1016/j.molstruc.2024.140562","DOIUrl":"10.1016/j.molstruc.2024.140562","url":null,"abstract":"<div><div>Secondary phenolic metabolites like flavonoids, that are found in numerous plant sections and have a range of uses. Quercetin falls under the category of flavonols, belonging to the flavonoids found in various medicinal plants, some common fruits, and vegetables with various applications. However, quercetin, with its various applications, is not well established in the pharmaceutical industry since it is associated with a lot of drawbacks, like instability in the gastrointestinal tract, the first-pass effect, solubility issues, etc. Quercetin-Schiff base derivatives are essential for targeting cancer cells and enhancing biological activities due to the formation of the C=N (imine group), which plays a major role in enhancing biological activities. In this research article, quercetin Schiff base (Q1sb) was synthesised and analysed using spectroscopic techniques like <sup>1</sup>H NMR, <sup>13</sup>C NMR, HRMS, etc. Biological activities like anti-bacterial, antioxidant, anti-inflammatory, and cytotoxicity analyses were done on four cancer cell lines, namely A549, HeLa, HepG2, and MCF-7, and molecular docking were done on some of the common targets. The first section explains the characteristics of flavonoid, the therapeutic action and drawbacks of quercetin, and the importance of Schiff base derivatives; the second section explains the synthesis method and characterization; and the third section explains the biological applications and molecular docking studies.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1322 ","pages":"Article 140562"},"PeriodicalIF":4.0,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657017","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 : 2024-11-03DOI: 10.1016/j.molstruc.2024.140579
Mohamed K. Elgohary , Mahmoud S. Elkotamy , Sara T. Al-Rashood , Faizah A. Binjubair , Renad S. Alarifi , Hazem A. Ghabbour , Wagdy M. Eldehna , Hatem A. Abdel-Aziz
Our study explored the anticancer potential of novel heterocyclic compounds, specifically 6a-d, 8a-d, 12a-d, and 13a-d, which are derived from imidazo[2,1-b]thiazole and imidazo[1,2-a]pyridine and linked through a hydrazide moiety. These compounds were assessed for their anticancer activity toward the MDA-MB-231 breast cancer cell line to evaluate their effectiveness in inhibiting cancer cell proliferation. Among the compounds tested, 13c and 13d emerged as the most active, with IC50 values of 4.40 ± 2.87 µM and 4.69 ± 2.55 µM, respectively. These two compounds were further investigated for their effects on VEGFR-2 enzymatic activity, cell cycle progression, and apoptosis, then 13c and 13d were further evaluated for their impact on DNA fragmentation using the comet assay. Both compounds demonstrated a significant increase in DNA fragmentation, with levels of damage being twice as high as those observed in the untreated control cells. Molecular docking studies through VEGFR-2 demonstrated that compounds 13c and 13d bind to VEGFR-2 in a manner comparable to the co-crystallized ligand sunitinib I. Further analysis using density functional theory highlighted their favorable physical properties. Additionally, computational evaluations of ADME and drug-likeness suggest that these derivatives hold promise and merit further investigation. The ultimate goal is to develop effective, safe, and orally bioavailable VEGFR-2 inhibitors for potential use in anticancer therapy.
{"title":"Exploring antitumor activity of novel imidazo[2,1-b]thiazole and imidazo[1,2-a]pyridine derivatives on MDA-MB-231 cell line: Targeting VEGFR-2 enzyme with computational insight","authors":"Mohamed K. Elgohary , Mahmoud S. Elkotamy , Sara T. Al-Rashood , Faizah A. Binjubair , Renad S. Alarifi , Hazem A. Ghabbour , Wagdy M. Eldehna , Hatem A. Abdel-Aziz","doi":"10.1016/j.molstruc.2024.140579","DOIUrl":"10.1016/j.molstruc.2024.140579","url":null,"abstract":"<div><div>Our study explored the anticancer potential of novel heterocyclic compounds, specifically <strong>6a-d, 8a-d, 12a-d</strong>, and <strong>13a-d</strong>, which are derived from imidazo[2,1-<em>b</em>]thiazole and imidazo[1,2-<em>a</em>]pyridine and linked through a hydrazide moiety. These compounds were assessed for their anticancer activity toward the MDA-MB-231 breast cancer cell line to evaluate their effectiveness in inhibiting cancer cell proliferation. Among the compounds tested, <strong>13c</strong> and <strong>13d</strong> emerged as the most active, with IC<sub>50</sub> values of 4.40 ± 2.87 µM and 4.69 ± 2.55 µM, respectively. These two compounds were further investigated for their effects on VEGFR-2 enzymatic activity, cell cycle progression, and apoptosis, then <strong>13c</strong> and <strong>13d</strong> were further evaluated for their impact on DNA fragmentation using the comet assay. Both compounds demonstrated a significant increase in DNA fragmentation, with levels of damage being twice as high as those observed in the untreated control cells. Molecular docking studies through VEGFR-2 demonstrated that compounds <strong>13c</strong> and <strong>13d</strong> bind to VEGFR-2 in a manner comparable to the co-crystallized ligand sunitinib <strong>I</strong>. Further analysis using density functional theory highlighted their favorable physical properties. Additionally, computational evaluations of ADME and drug-likeness suggest that these derivatives hold promise and merit further investigation. The ultimate goal is to develop effective, safe, and orally bioavailable VEGFR-2 inhibitors for potential use in anticancer therapy.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1322 ","pages":"Article 140579"},"PeriodicalIF":4.0,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657289","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 : 2024-11-03DOI: 10.1016/j.molstruc.2024.140596
Lei Cao , Behnaz Abdi , Ning Ma , Hongwei Liu , Chunyan Zhang , Pengfei Lv , Juan Zhang
Chromeno[4,3-b]chromenes have shown potential as effective drugs against cardiovascular diseases, primarily due to their diverse biological activities, including anti-inflammatory and antioxidant properties. This study was conducted on a new heterojunction nanocomposite TiO2/ZnWO3 consisting of titanium dioxide (TiO2) and zinc tungstate (ZnWO3) with enhanced photocatalytic capability. TiO2/ZnWO3 nanophotocatalyst is characterized by FT-IR, XRD, DRS, SEM, and EDX and performed as an efficient nanophotocatalyst in the synthesis of chromeno[4,3-b]chromene derivatives. The research focused on the intricate interplay of the components, aiming to optimize the catalytic reactions under green-light irradiation. Through this investigation, insights were gained into the mechanistic pathways and the potential for improved yields in the formation of the desired chromene. TiO2 has the ability to absorb light and produce electrons and holes when exposed to the direct light; but to increase its photocatalytic activity, an additional component ZnWO3 is combined. Effect of photocatalyst amount, reaction time, temperature, and solvent as well as reusability of the nanocomposite are investigated. The research focused on the intricate interplay of the components, aiming to optimize the catalytic reactions under green-light irradiation. Through this investigation, insights were gained into the mechanistic pathways and the potential for improved yields in the formation of the desired chromene. TiO2 has the ability to absorb light and produce electrons and holes when exposed to the direct light; but to increase its photocatalytic activity, an additional component ZnWO3 is combined. Effect of photocatalyst amount, reaction time, temperature, and solvent as well as reusability of the nanocomposite are investigated.
{"title":"TiO2/ZnWO3 with improved photocatalytic performance in the preparation of chromeno[4,3-b]chromenes, as cardiovascular drugs","authors":"Lei Cao , Behnaz Abdi , Ning Ma , Hongwei Liu , Chunyan Zhang , Pengfei Lv , Juan Zhang","doi":"10.1016/j.molstruc.2024.140596","DOIUrl":"10.1016/j.molstruc.2024.140596","url":null,"abstract":"<div><div>Chromeno[4,3-b]chromenes have shown potential as effective drugs against cardiovascular diseases, primarily due to their diverse biological activities, including anti-inflammatory and antioxidant properties. This study was conducted on a new heterojunction nanocomposite TiO<sub>2</sub>/ZnWO<sub>3</sub> consisting of titanium dioxide (TiO<sub>2</sub>) and zinc tungstate (ZnWO<sub>3</sub>) with enhanced photocatalytic capability. TiO<sub>2</sub>/ZnWO<sub>3</sub> nanophotocatalyst is characterized by FT-IR, XRD, DRS, SEM, and EDX and performed as an efficient nanophotocatalyst in the synthesis of chromeno[4,3-b]chromene derivatives. The research focused on the intricate interplay of the components, aiming to optimize the catalytic reactions under green-light irradiation. Through this investigation, insights were gained into the mechanistic pathways and the potential for improved yields in the formation of the desired chromene. TiO<sub>2</sub> has the ability to absorb light and produce electrons and holes when exposed to the direct light; but to increase its photocatalytic activity, an additional component ZnWO<sub>3</sub> is combined. Effect of photocatalyst amount, reaction time, temperature, and solvent as well as reusability of the nanocomposite are investigated. The research focused on the intricate interplay of the components, aiming to optimize the catalytic reactions under green-light irradiation. Through this investigation, insights were gained into the mechanistic pathways and the potential for improved yields in the formation of the desired chromene. TiO<sub>2</sub> has the ability to absorb light and produce electrons and holes when exposed to the direct light; but to increase its photocatalytic activity, an additional component ZnWO<sub>3</sub> is combined. Effect of photocatalyst amount, reaction time, temperature, and solvent as well as reusability of the nanocomposite are investigated.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1322 ","pages":"Article 140596"},"PeriodicalIF":4.0,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142656917","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 : 2024-11-03DOI: 10.1016/j.molstruc.2024.140530
Yuehua He , Mithun Kumar Ghosh , Ren-Min Ma , Lu Lu , Shulan Cai , Mohd Afzal , Abdullah Alarifi , Tanmay Kumar Ghorai
A new coordination polymer (CP), {[Zn(HL)₂(bib)]ₙ.0·25H2O} (1), was synthesized and characterized for its structural, thermal, and luminescence properties. The compound was obtained by reacting H3L= 3-(4-carboxyphenoxy)-5-methylbenzoic acid, bib = 1,4-bis(1-imidazoly)benzene, and Zn(ClO₄)₂·6H₂O in aqueous solution, followed by hydrothermal treatment at 120 °C for 72 h. Single-crystal X-ray diffraction revealed a 1D polymeric chain with zinc centres in a distorted tetrahedral geometry, coordinated by carboxylate and imidazole-based ligands. Infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA) confirmed the bonding environment and thermal stability. CP 1 exhibited strong luminescence, peaking at 205 nm upon excitation at 285 nm, and demonstrated selective sensing of ascorbic acid (AA) with a high quenching efficiency (Ksv = 4.35 × 10² M⁻¹) and a detection limit of 3.15 × 10⁻4 M The luminescence was pH-dependent, with optimal fluorescence near neutral pH. These findings highlight the potential of CP 1 as a sensitive probe for AA detection, offering applications in environmental monitoring and chemical sensing.
{"title":"A tetrahedral zinc(II) coordination polymer: Synthesis, characterisation, and application in ascorbic Acid fluorescence sensing","authors":"Yuehua He , Mithun Kumar Ghosh , Ren-Min Ma , Lu Lu , Shulan Cai , Mohd Afzal , Abdullah Alarifi , Tanmay Kumar Ghorai","doi":"10.1016/j.molstruc.2024.140530","DOIUrl":"10.1016/j.molstruc.2024.140530","url":null,"abstract":"<div><div>A new coordination polymer (CP), {[Zn(HL)₂(bib)]ₙ.0·25H<sub>2</sub>O} (<strong>1</strong>), was synthesized and characterized for its structural, thermal, and luminescence properties. The compound was obtained by reacting H<sub>3</sub>L= 3-(4-carboxyphenoxy)-5-methylbenzoic acid, bib = 1,4-bis(1-imidazoly)benzene, and Zn(ClO₄)₂·6H₂O in aqueous solution, followed by hydrothermal treatment at 120 °C for 72 h. Single-crystal X-ray diffraction revealed a 1D polymeric chain with zinc centres in a distorted tetrahedral geometry, coordinated by carboxylate and imidazole-based ligands. Infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA) confirmed the bonding environment and thermal stability. <strong>CP 1</strong> exhibited strong luminescence, peaking at 205 nm upon excitation at 285 nm, and demonstrated selective sensing of ascorbic acid (AA) with a high quenching efficiency (<em>K</em><sub>sv</sub> = 4.35 × 10² M⁻¹) and a detection limit of 3.15 × 10<sup>⁻4</sup> M The luminescence was pH-dependent, with optimal fluorescence near neutral pH. These findings highlight the potential of <strong>CP 1</strong> as a sensitive probe for AA detection, offering applications in environmental monitoring and chemical sensing.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1322 ","pages":"Article 140530"},"PeriodicalIF":4.0,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142572093","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 : 2024-11-02DOI: 10.1016/j.molstruc.2024.140547
Jian-Di Lin , Fa-Kun Zheng
Heat-resistant explosives are pivotal for specialized applications demanding high thermal stability, essential in both civil and military sectors, especially in extreme environments. Our study focuses on the synthesis of a 3D nitrogen-rich supramolecular energetic metal-organic framework (MOF), Zn(ATZ)2 (1), using the 5-aminotetrazole (HATZ) ligand and Zn(II) ion. Structural analysis indicates that compound 1 adopts the orthorhombic CmCm space group and possesses a robust 2D network, characterized by strong π-π packing interactions between 2D layers, offering exceptional thermal stability up to 322 °C with minimal mechanical sensitivity. The standard molar enthalpy of formation (ΔfHo) and heat of detonation (ΔHdet) for compound 1 are calculated to be 7.08 kJ/g and 7.34 kJ/g, respectively. Remarkably, the ΔfHo of compound 1 significantly exceeds those of traditional heat-resistant explosives like RDX (0.32 kJ/g), HNS (0.17 kJ/g), TNT (–0.295 kJ/g), and TATB (–0.54 kJ/g), and is also higher than those of most reported energetic MOF materials. Similarly, its ΔHdet value surpasses those of common explosives such as TNT (4.144 kJ/g), HMX (5.525 kJ/g) and RDX (5.71 kJ/g), as well as the majority of reported energetic MOFs. Compound 1 also demonstrates impressive detonation properties with a velocity (D) of 7.22 km s-1 and a pressure (P) of 21.95 GPa, outperforming many other energetic MOF materials. These superior energetic characteristics position compound 1 as a strong candidate for heat-resistant explosives, showcasing its potential for future applications in demanding environments.
{"title":"A 3D nitrogen-rich heat-resistant supramolecular MOF with superior energetic performances assembled from Zn(II) and 5-aminotetrazole","authors":"Jian-Di Lin , Fa-Kun Zheng","doi":"10.1016/j.molstruc.2024.140547","DOIUrl":"10.1016/j.molstruc.2024.140547","url":null,"abstract":"<div><div>Heat-resistant explosives are pivotal for specialized applications demanding high thermal stability, essential in both civil and military sectors, especially in extreme environments. Our study focuses on the synthesis of a 3D nitrogen-rich supramolecular energetic metal-organic framework (MOF), Zn(ATZ)<sub>2</sub> (<strong>1</strong>), using the 5-aminotetrazole (HATZ) ligand and Zn(II) ion. Structural analysis indicates that compound <strong>1</strong> adopts the orthorhombic <em>CmCm</em> space group and possesses a robust 2D network, characterized by strong π-π packing interactions between 2D layers, offering exceptional thermal stability up to 322 °C with minimal mechanical sensitivity. The standard molar enthalpy of formation (<em>Δ<sub>f</sub>H<sup>o</sup></em>) and heat of detonation (<em>ΔH<sub>det</sub></em>) for compound <strong>1</strong> are calculated to be 7.08 kJ/g and 7.34 kJ/g, respectively. Remarkably, the <em>Δ<sub>f</sub>H<sup>o</sup></em> of compound <strong>1</strong> significantly exceeds those of traditional heat-resistant explosives like RDX (0.32 kJ/g), HNS (0.17 kJ/g), TNT (–0.295 kJ/g), and TATB (–0.54 kJ/g), and is also higher than those of most reported energetic MOF materials. Similarly, its <em>ΔH<sub>det</sub></em> value surpasses those of common explosives such as TNT (4.144 kJ/g), HMX (5.525 kJ/g) and RDX (5.71 kJ/g), as well as the majority of reported energetic MOFs. Compound <strong>1</strong> also demonstrates impressive detonation properties with a velocity (<em>D</em>) of 7.22 km s<sup>-1</sup> and a pressure (<em>P</em>) of 21.95 GPa, outperforming many other energetic MOF materials. These superior energetic characteristics position compound <strong>1</strong> as a strong candidate for heat-resistant explosives, showcasing its potential for future applications in demanding environments.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1322 ","pages":"Article 140547"},"PeriodicalIF":4.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657228","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}
The aim of this work is the in vitro determination of the immunomodulation effect of pyrano[3,2-c]chromenes on the proliferation of T lymphocyts. These tricyclic heterocycles were prepared at room temperature via a one-pot, three-component condensation reaction involving 4‑hydroxy-2H-chromen-2-one, aromatic aldehydes, and malononitrile, using morpholine as a catalyst in a 1:1 ethanol/water mixture. This multicomponent reaction affords the product in high yields, in accordance with the criteria of green chemistry. The structure elucidation was accomplished by spectral data, IR, NMR (1H, 13C, 2D). We determined the in vitro effects of 2-amino-4-(3‑hydroxy-5-methoxyphenyl)-5-oxo-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile (AC09) the 2-amino-5-oxo-4-(thiophen-2-yl)-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile (AC11) derivatives, on the proliferative responses of human T lymphocyts cells, cytokine secretion and intracellular redox status. The study revealed that compounds AC09 and AC11 are efficient immunostimulants in a dose-dependent manner.
Human lymphocytes were less sensitive to AC11 at high concentrations compared to the potency of AC09. Human lymphocyte IL-2, IFNγ and IL-4 secretions were significantly enhanced by those pyrano[3,2-c]chromenes derivatives in a dose-dependent manner. The levels of intracellular lymphocytes glutathione (GSH), were unaffected by AC09 and AC11 at any concentrations. AC09 and AC11 induce a significant increase in hydroperoxide and carbonyl protein contents at high concentrations. Conversely, a computational study using molecular modelling revealed that compounds AC09 and AC11 exhibit a strong affinity for the active site residues of Interferon-γ (IFN-γ; PDB ID: 6E3K) target. This is confirmed by the low score energy value and the formation of different types of interactions such as: hydrogen bonds, hydrophobic interactions, and van der Waals forces. Moreover, all Drug likeness's rules were validated, and no toxicity is presented by these compounds. Finally, in vitro studies, molecular docking techniques and ADME-T (Absorption, Distribution, Metabolism, Excretion and Toxicity) evaluations were successfully conducted, aiding in the identification of new IFN-γ target inhibitors. A comparative analysis /or studies was then carried out to highlight the complementary effects of the two approaches.
{"title":"One-pot synthesis of tricyclic pyrano[3.2-c]chromene derivatives and their evaluation through in vitro immunomodulatory activity against T cells; Molecular docking investigations and ADME-Tox prediction studies","authors":"Ahmed Chelihi , Amel Medjdoub Tahir , Ridha Hassaine , Ismail Daoud , Mohammed Benabdallah , Amel Zoubeyda Merzouk , Hafida Merzouk , Noureddine Choukchou-Braham , Nadia Taibi","doi":"10.1016/j.molstruc.2024.140554","DOIUrl":"10.1016/j.molstruc.2024.140554","url":null,"abstract":"<div><div>The aim of this work is the <em>in vitro</em> determination of the immunomodulation effect of pyrano[3,2-<em>c</em>]chromenes on the proliferation of T lymphocyts. These tricyclic heterocycles were prepared at room temperature via a one-pot, three-component condensation reaction involving 4‑hydroxy-2<em>H</em>-chromen-2-one, aromatic aldehydes, and malononitrile, using morpholine as a catalyst in a 1:1 ethanol/water mixture. This multicomponent reaction affords the product in high yields, in accordance with the criteria of green chemistry. The structure elucidation was accomplished by spectral data, IR, NMR (<sup>1</sup>H, <sup>13</sup>C, 2D). We determined the <em>in vitro</em> effects of 2-amino-4-(3‑hydroxy-5-methoxyphenyl)-5-oxo-4<em>H</em>,5<em>H</em>-pyrano[3,2-<em>c</em>]chromene-3-carbonitrile (<strong>AC09</strong>) the 2-amino-5-oxo-4-(thiophen-2-yl)-4<em>H</em>,5<em>H</em>-pyrano[3,2-<em>c</em>]chromene-3-carbonitrile (<strong>AC11</strong>) derivatives, on the proliferative responses of human T lymphocyts cells, cytokine secretion and intracellular redox status. The study revealed that compounds AC09 and AC11 are efficient immunostimulants in a dose-dependent manner.</div><div>Human lymphocytes were less sensitive to AC11 at high concentrations compared to the potency of AC09. Human lymphocyte IL-2, IFNγ and IL-4 secretions were significantly enhanced by those pyrano[3,2-c]chromenes derivatives in a dose-dependent manner. The levels of intracellular lymphocytes glutathione (GSH), were unaffected by <strong>AC09</strong> and <strong>AC11</strong> at any concentrations. <strong>AC09</strong> and <strong>AC11</strong> induce a significant increase in hydroperoxide and carbonyl protein contents at high concentrations. Conversely, a computational study using molecular modelling revealed that compounds <strong>AC09</strong> and <strong>AC11</strong> exhibit a strong affinity for the active site residues of Interferon-γ (IFN-γ; PDB ID: <span><span>6E3K</span><svg><path></path></svg></span>) target. This is confirmed by the low score energy value and the formation of different types of interactions such as: hydrogen bonds, hydrophobic interactions, and van der Waals forces. Moreover, all Drug likeness's rules were validated, and no toxicity is presented by these compounds. Finally, <em>in vitro</em> studies, molecular docking techniques and ADME-T (Absorption, Distribution, Metabolism, Excretion and Toxicity) evaluations were successfully conducted, aiding in the identification of new IFN-<em>γ</em> target inhibitors. A comparative analysis /or studies was then carried out to highlight the complementary effects of the two approaches.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1322 ","pages":"Article 140554"},"PeriodicalIF":4.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657287","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 : 2024-11-02DOI: 10.1016/j.molstruc.2024.140565
Qingkun Wu , Jingxuan Hou , Qingshan Gu , Meiqi Shi , Lu Zheng
G protein-coupled receptor 52 (GPR52) is considered to be a promising target to improve the symptoms of psychiatric disorders and its agonists are expected to treat schizophrenia without traditional side effects. Several research institutions have reported some small molecule GPR52 agonists, which can be the starting point for rational drug development. In this study, a series of N-arylindole derivatives were designed and synthesized based on 3g according to classical pharmacochemical methods and computer aided drug design (CADD). The designed compounds exhibited good to excellent activities and the structure-activity relationship (SAR) study was explored. The results show that the connection mode between the hydrophilic head (Part I) and the indole ring (Part II) plays an important role in the GPR52 agonist activity. Among these compounds, compounds 16 and 21 have good GPR52 agonist activity (EC50 = 93 nM and 75 nM) and can inhibit hyperactive behavior in mice induced by MK-801 (EC50 =7.94 mg/kg and 6.64 mg/kg). These designed small molecules will provide new options for the development of novel GPR52 agonists.
{"title":"Molecular modeling aided design, synthesis, and activity evaluation of N-arylindole derivatives as GPR52 agonists","authors":"Qingkun Wu , Jingxuan Hou , Qingshan Gu , Meiqi Shi , Lu Zheng","doi":"10.1016/j.molstruc.2024.140565","DOIUrl":"10.1016/j.molstruc.2024.140565","url":null,"abstract":"<div><div>G protein-coupled receptor 52 (GPR52) is considered to be a promising target to improve the symptoms of psychiatric disorders and its agonists are expected to treat schizophrenia without traditional side effects. Several research institutions have reported some small molecule GPR52 agonists, which can be the starting point for rational drug development. In this study, a series of <em>N</em>-arylindole derivatives were designed and synthesized based on <strong>3g</strong> according to classical pharmacochemical methods and computer aided drug design (CADD). The designed compounds exhibited good to excellent activities and the structure-activity relationship (SAR) study was explored. The results show that the connection mode between the hydrophilic head (Part I) and the indole ring (Part II) plays an important role in the GPR52 agonist activity. Among these compounds, compounds <strong>16</strong> and <strong>21</strong> have good GPR52 agonist activity (EC<sub>50</sub> = 93 nM and 75 nM) and can inhibit hyperactive behavior in mice induced by MK-801 (EC<sub>50</sub> =7.94 mg/kg and 6.64 mg/kg). These designed small molecules will provide new options for the development of novel GPR52 agonists.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1322 ","pages":"Article 140565"},"PeriodicalIF":4.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587096","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 : 2024-11-02DOI: 10.1016/j.molstruc.2024.140558
Alia Mushtaq, Muhammad Moazzam Naseer
The ongoing challenge of cancer in modern medicine highlights the urgent need for targeted therapeutic strategies, particularly against the EGFR/PI3K/AKT/mTOR signalling pathways, which are pivotal in tumorigenesis. This study presents the design, synthesis, characterization, DNA binding studies and computational evaluation of a novel series of trisubstituted s-triazine derivatives 3a–n as potential anticancer agents. The synthetic methodology utilized the reaction of various oxygen-containing nucleophiles with cyanuric chloride via nucleophilic aromatic substitution, yielding the corresponding target products with high yield and purity. Density Functional Theory (DFT) calculations utilizing the B3LYP level provided insights into the electronic properties of the compounds, with derivatives 3f, 3n, and 3l displaying the lowest energy gaps and highest electrophilicity indices, indicative of their enhanced reactivity. DNA binding results from UV–Vis absorption spectroscopy confirmed the groove mode of binding for the most potent compound 3f with the binding constant (Kb) value of 6.75 × 104 M−1. Molecular docking studies against DNA (PDB ID: 3EY0) and EGFR (PDB ID: 6V6O) revealed strong binding affinities, with compound 3f (R1= ethoxy, R2= 3-CF3) exhibiting a notable binding energy of -8.9 kcal/mol and −9.1 kcal/mol respectively. Additionally, these compounds showed significant binding interactions with PI3K (PDB ID: 5HJB) and mTOR (PDB ID: 4JSV), suggesting their potential as dual inhibitors of the PI3K/AKT/mTOR pathway. The drug-likeness and ADMET profiles further support the therapeutic promise of compound 3f bearing a 3-trifluoromethyl substituent.
{"title":"Novel s-triazine derivatives as potential anticancer agents: Synthesis, DFT, DNA binding, molecular docking, MD simulation and in silico ADMET profiling","authors":"Alia Mushtaq, Muhammad Moazzam Naseer","doi":"10.1016/j.molstruc.2024.140558","DOIUrl":"10.1016/j.molstruc.2024.140558","url":null,"abstract":"<div><div>The ongoing challenge of cancer in modern medicine highlights the urgent need for targeted therapeutic strategies, particularly against the EGFR/PI3K/AKT/mTOR signalling pathways, which are pivotal in tumorigenesis. This study presents the design, synthesis, characterization, DNA binding studies and computational evaluation of a novel series of trisubstituted <em>s</em>-triazine derivatives <strong>3a–n</strong> as potential anticancer agents. The synthetic methodology utilized the reaction of various oxygen-containing nucleophiles with cyanuric chloride via nucleophilic aromatic substitution, yielding the corresponding target products with high yield and purity. Density Functional Theory (DFT) calculations utilizing the B3LYP level provided insights into the electronic properties of the compounds, with derivatives <strong>3f, 3n,</strong> and <strong>3l</strong> displaying the lowest energy gaps and highest electrophilicity indices, indicative of their enhanced reactivity. DNA binding results from UV–Vis absorption spectroscopy confirmed the groove mode of binding for the most potent compound <strong>3f</strong> with the binding constant (K<sub>b</sub>) value of 6.75 × 10<sup>4</sup> M<sup>−1</sup>. Molecular docking studies against DNA (PDB ID: <span><span>3EY0</span><svg><path></path></svg></span>) and EGFR (PDB ID: <span><span>6V6O</span><svg><path></path></svg></span>) revealed strong binding affinities, with compound <strong>3f</strong> (R<sub>1</sub>= ethoxy, R<sub>2</sub>= 3-CF<sub>3</sub>) exhibiting a notable binding energy of -8.9 kcal/mol and −9.1 kcal/mol respectively. Additionally, these compounds showed significant binding interactions with PI3K (PDB ID: <span><span>5HJB</span><svg><path></path></svg></span>) and mTOR (PDB ID: <span><span>4JSV</span><svg><path></path></svg></span>), suggesting their potential as dual inhibitors of the PI3K/AKT/mTOR pathway. The drug-likeness and ADMET profiles further support the therapeutic promise of compound <strong>3f</strong> bearing a 3-trifluoromethyl substituent.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1322 ","pages":"Article 140558"},"PeriodicalIF":4.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657022","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 : 2024-11-02DOI: 10.1016/j.molstruc.2024.140590
K.J. Rajimon , Hamed A. El-Serehy , Neha Kannan , Renjith Thomas
This study thoroughly analyses the structural and biological properties of a Schiff base compound synthesized from the condensation of 2-formyl phenol and 4-chloroaniline. Single crystal X-ray diffraction examination indicated that the compound crystallizes in the monoclinic space group P21/c, with unit cell parameters a = 13.4232(15) Å, b = 5.7860(6) Å, c = 14.699(2) Å, β = 106.048(6) °, and Z = 4. The molecular structure has an E configuration around the C = N double bond, with a bond length of 1.266(2) Å, and includes an intramolecular O—H⋯N hydrogen bond. Hirshfeld surface analysis elucidated intermolecular interactions inside the crystal lattice, emphasizing dominant hydrogen-hydrogen, hydrogen-chlorine, and carbon-hydrogen contacts. The chemical exhibited concentration-dependent antioxidant and anti-inflammatory effects. Studies on DNA interactions indicate van der Waals forces between the ligand and nucleic acid, whereas it demonstrated considerable binding affinity for BSA with a ΔG value of -6.9 kcal/mol. ADME study revealed values within the recommended range, indicating advantageous pharmacokinetic characteristics. PASS filter-based cytotoxicity predictions indicated significant anti-cancer efficacy against breast adenocarcinoma, small cell lung carcinoma, and lung cancer. Toxicological assessments in diverse models indicated no possible irritation to skin and ocular tissues, highlighting its safety profile for therapeutic use. This research advances our comprehension of Schiff bases with halogen substituents and their prospective uses in chemistry and biology.
本研究深入分析了一种由 2-甲酰基苯酚和 4-氯苯胺缩合合成的希夫碱化合物的结构和生物特性。单晶 X 射线衍射检查表明，该化合物结晶于单斜空间群 P21/c，单胞参数 a = 13.4232(15) Å，b = 5.7860(6) Å，c = 14.699(2) Å，β = 106.048(6) °，Z = 4。分子结构围绕 C = N 双键呈 E 型构型，键长为 1.266(2) Å，并包含一个分子内 O-H⋯N 氢键。Hirshfeld 表面分析阐明了晶格内的分子间相互作用，强调了主要的氢-氢、氢-氯和碳-氢接触。这种化学物质具有浓度依赖性的抗氧化和抗炎作用。对 DNA 相互作用的研究表明，配体与核酸之间存在范德华力，而它与 BSA 的结合亲和力相当高，ΔG 值为 -6.9 kcal/mol。ADME 研究显示，其值在推荐范围内，表明其具有良好的药代动力学特性。基于 PASS 过滤器的细胞毒性预测表明，该药物对乳腺癌、小细胞肺癌和肺癌具有显著的抗癌功效。在不同模型中进行的毒理学评估表明，该化合物不会对皮肤和眼部组织产生刺激，从而突出了其治疗用途的安全性。这项研究加深了我们对带有卤素取代基的希夫碱及其在化学和生物学中的应用前景的理解。
{"title":"Comprehensive assessment of schiff base derived from 4-Chloroaniline and 2-Formylphenol: Molecular architecture, experimental with computational bioactivity profiling, emphasizing anticancer efficacy against pulmonary and mammary carcinoma cell models","authors":"K.J. Rajimon , Hamed A. El-Serehy , Neha Kannan , Renjith Thomas","doi":"10.1016/j.molstruc.2024.140590","DOIUrl":"10.1016/j.molstruc.2024.140590","url":null,"abstract":"<div><div>This study thoroughly analyses the structural and biological properties of a Schiff base compound synthesized from the condensation of 2-formyl phenol and 4-chloroaniline. Single crystal X-ray diffraction examination indicated that the compound crystallizes in the monoclinic space group P21/c, with unit cell parameters <em>a</em> = 13.4232(15) Å, <em>b</em> = 5.7860(6) Å, <em>c</em> = 14.699(2) Å, β = 106.048(6) °, and <em>Z</em> = 4. The molecular structure has an E configuration around the C = N double bond, with a bond length of 1.266(2) Å, and includes an intramolecular O—H⋯N hydrogen bond. Hirshfeld surface analysis elucidated intermolecular interactions inside the crystal lattice, emphasizing dominant hydrogen-hydrogen, hydrogen-chlorine, and carbon-hydrogen contacts. The chemical exhibited concentration-dependent antioxidant and anti-inflammatory effects. Studies on DNA interactions indicate van der Waals forces between the ligand and nucleic acid, whereas it demonstrated considerable binding affinity for BSA with a ΔG value of -6.9 kcal/mol. ADME study revealed values within the recommended range, indicating advantageous pharmacokinetic characteristics. PASS filter-based cytotoxicity predictions indicated significant anti-cancer efficacy against breast adenocarcinoma, small cell lung carcinoma, and lung cancer. Toxicological assessments in diverse models indicated no possible irritation to skin and ocular tissues, highlighting its safety profile for therapeutic use. This research advances our comprehension of Schiff bases with halogen substituents and their prospective uses in chemistry and biology.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1322 ","pages":"Article 140590"},"PeriodicalIF":4.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142656914","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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