In this research, the preparation of new (methylsulfonyl)pyrano[3,2-c]quinolone, and pyrano[3,2-c]quinoline-3-carbonitrile derivatives using starting materials including 1-methylquinoline-2,4-dione, methylsulfonylacetonitrile or malononitrile, and aromatic aldehydes in the presence of [Triazolamine][Acetate] as ionic liquid catalyst were described. A simple and green method for the synthesis of novel organic compounds in H2O as solvent under reflux temperature conditions using a green and recyclable ionic liquid as catalyst is reported. The synthesis of diverse and new pyrano[3,2-c]quinoline derivatives, easy work-up procedure, high yields of products, short reaction times, use of green solvent, easy recovery and separation of the catalyst are the advantages of this protocol.
{"title":"Synthesis of New (Methylsulfonyl)Pyrano[3,2-c]Quinoline and Pyrano[3,2-c]Quinoline-3-Carbonitrile Derivatives Using [Triazolamine][Acetate] as a Basic Ionic Liquid Catalyst","authors":"Farhad Shirzaei (Conceptualization Data curation Formal analysis Investigation Methodology Project administration Resources Software Supervision Writing – original draft Writing – review & editing) , Hamid Reza Shaterian (Conceptualization Data curation Formal analysis Investigation Methodology Project administration Resources Software Supervision Writing – original draft Writing – review & editing)","doi":"10.1080/10406638.2025.2563102","DOIUrl":"10.1080/10406638.2025.2563102","url":null,"abstract":"<div><div>In this research, the preparation of new (methylsulfonyl)pyrano[3,2-<em>c</em>]quinolone, and pyrano[3,2-<em>c</em>]quinoline-3-carbonitrile derivatives using starting materials including 1-methylquinoline-2,4-dione, methylsulfonylacetonitrile or malononitrile, and aromatic aldehydes in the presence of [Triazolamine][Acetate] as ionic liquid catalyst were described. A simple and green method for the synthesis of novel organic compounds in H<sub>2</sub>O as solvent under reflux temperature conditions using a green and recyclable ionic liquid as catalyst is reported. The synthesis of diverse and new pyrano[3,2-<em>c</em>]quinoline derivatives, easy work-up procedure, high yields of products, short reaction times, use of green solvent, easy recovery and separation of the catalyst are the advantages of this protocol.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 10","pages":"Pages 2152-2165"},"PeriodicalIF":2.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Two significant worldwide health issues that call for the creation of new therapeutic medicines are oxidative stress and antibiotic resistance. Quinazolinone-1,2,4-triazole derivatives, which have a variety of pharmacological characteristics, may be able to help with these problems. As possible antibacterial and anticancer targets, this study sought to synthesized novel quinazoline-4(3H)-one derivatives containing an NH group at position 3 with 1,2,4-triazoles (7a–7k). The chemical structures of all compounds were characterized by NMR (1H/13C), IR and mass spectroscopy. Notably, derivatives 7d and 7e exhibited the greatest MIC values against S. epidermidis, while 7f was the best against S. aureus with MIC of 3.5 μg mL−1, two-fold efficacy more than that was recorded with moxifloxacin. All of the synthesized compounds showed promising anti-proliferative activity, with one compounds 7e having potent cytotoxic activity against MDA-MB-231 cell line (IC50 = 11.80 ± 1.2 μM) and active against MCF-7 (IC50 = 11.80 ± 1.2 μM respectively) in comparison to the reference DXN (IC50 = 9.48 ± 0.6 and 7.12 ± 2.0 μM, respectively). Molecular docking was performed using the protein structure of E. coli Topoisomerase IV, with the interacting effectively with key residues IleA:116, SerA:117, ArgA:93, GluA:46, ThrA:163, and GlyA:71, consistent with their antimicrobial activity. The chemical nature of these compounds was revealed by performing the density functional theory (DFT) calculation using hybrid B3LYP functional with 6-31 g(d) basis set. Additionally, these compounds exhibited promising physicochemical properties, paving the way for discovering new antimicrobial drugs.
{"title":"Design, Synthesis, Molecular Docking, ADME/Tox Predictions and DFT Study of Quinazolinone-1,2,4-Triazole Analogues as Promising Antimicrobial Agents","authors":"Areveli Srinivas (Data curation Methodology Validation) , Jaya Shree Anireddy (Supervision Writing – review & editing) , Bhoomandla Srinu (Formal analysis Resources Software) , Konda Santosh Kumar (Conceptualization Data curation Resources Validation) , Gajula Ramesh Kumar (Formal analysis Resources) , Ramya Gollamudi (Formal analysis Validation Visualization)","doi":"10.1080/10406638.2025.2551225","DOIUrl":"10.1080/10406638.2025.2551225","url":null,"abstract":"<div><div>Two significant worldwide health issues that call for the creation of new therapeutic medicines are oxidative stress and antibiotic resistance. Quinazolinone-1,2,4-triazole derivatives, which have a variety of pharmacological characteristics, may be able to help with these problems. As possible antibacterial and anticancer targets, this study sought to synthesized novel quinazoline-4(3H)-one derivatives containing an NH group at position 3 with 1,2,4-triazoles (<strong>7a–7k</strong>). The chemical structures of all compounds were characterized by NMR (<sup>1</sup>H/<sup>13</sup>C), IR and mass spectroscopy. Notably, derivatives <strong>7d</strong> and <strong>7e</strong> exhibited the greatest MIC values against <em>S. epidermidis</em>, while <strong>7f</strong> was the best against <em>S. aureus</em> with MIC of 3.5 μg mL<sup>−1</sup>, two-fold efficacy more than that was recorded with moxifloxacin. All of the synthesized compounds showed promising anti-proliferative activity, with one compounds <strong>7e</strong> having potent cytotoxic activity against MDA-MB-231 cell line (IC<sub>50</sub> = 11.80 ± 1.2 μM) and active against MCF-7 (IC<sub>50</sub> = 11.80 ± 1.2 μM respectively) in comparison to the reference DXN (IC<sub>50</sub> = 9.48 ± 0.6 and 7.12 ± 2.0 μM, respectively). Molecular docking was performed using the protein structure of <em>E. coli</em> Topoisomerase IV, with the interacting effectively with key residues IleA:116, SerA:117, ArgA:93, GluA:46, ThrA:163, and GlyA:71, consistent with their antimicrobial activity. The chemical nature of these compounds was revealed by performing the density functional theory (DFT) calculation using hybrid B3LYP functional with 6-31 g(d) basis set. Additionally, these compounds exhibited promising physicochemical properties, paving the way for discovering new antimicrobial drugs.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 10","pages":"Pages 2002-2021"},"PeriodicalIF":2.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer is a serious health issue that has affected people of all ages and everywhere for a long time. In view of it a library of thiazole—tetrahydropyridine—pyridine derivatives synthesized evaluated for their in vitro anticancer activity against human breast adenocarcinoma (MCF-7) and human lung cancer (A-549) cell lines, using Doxorubicin as the standard reference. The compound 6k with -F and -CH3 substituents found to be more potent with IC50 value of 8.72 ± 0.88 µM and 8.54 ± 0.85 µM against MCF-7 and A-549 cells, respectively, compound 6c containing trifluoromethoxy group as substituent with IC50 value of 9.45 ± 1.02 µM (MCF-7) and 9.59 ± 1.08 µM (A-549), compound 6 g with trifluoromethyl and methyl substituents presented prominent activity with IC50 value of 11.19 ± 1.03 µM (MCF-7) and 11.34 ± 1.07 µM (A-549) and compound 6 m with trifluoromethyl group showed good activity with IC50 value of 14.54 ± 1.03 µM (MCF-7) and 14.35 ± 1.05 µM (A-549). The toxicity test against Hek-293 revealed that they are not harmful to normal cells. Molecular docking study of potent ligand 6k revealed their best dock score and promising binding interactions. Presented ADME prediction of all compounds.
{"title":"Design, Synthesis, Cytotoxicity, and Molecular Docking of New Thiazole Linked Tetrahydropyridine: Pyridine Hybrids","authors":"Ram Mohan Malothu (Data curation Visualization) , Gangadhar Thalari (Data curation Visualization)","doi":"10.1080/10406638.2025.2554200","DOIUrl":"10.1080/10406638.2025.2554200","url":null,"abstract":"<div><div>Cancer is a serious health issue that has affected people of all ages and everywhere for a long time. In view of it a library of thiazole—tetrahydropyridine—pyridine derivatives synthesized evaluated for their <em>in vitro</em> anticancer activity against human breast adenocarcinoma (MCF-7) and human lung cancer (A-549) cell lines, using <em>Doxorubicin</em> as the standard reference. The compound <strong>6k</strong> with -F and -CH<sub>3</sub> substituents found to be more potent with IC<sub>50</sub> value of <strong>8.72 ± 0.88 µM</strong> and <strong>8.54 ± 0.85 µM</strong> against MCF-7 and A-549 cells, respectively, compound <strong>6c</strong> containing trifluoromethoxy group as substituent with IC<sub>50</sub> value of <strong>9.45 ± 1.02 µM</strong> (MCF-7) and <strong>9.59 ± 1.08 µM</strong> (A-549), compound <strong>6 g</strong> with trifluoromethyl and methyl substituents presented prominent activity with IC<sub>50</sub> value of <strong>11.19 ± 1.03 µM</strong> (MCF-7) and <strong>11.34 ± 1.07 µM</strong> (A-549) and compound <strong>6 m</strong> with trifluoromethyl group showed good activity with IC<sub>50</sub> value of <strong>14.54 ± 1.03 µM</strong> (MCF-7) and <strong>14.35 ± 1.05 µM</strong> (A-549). The toxicity test against Hek-293 revealed that they are not harmful to normal cells. Molecular docking study of potent ligand <strong>6k</strong> revealed their best dock score and promising binding interactions. Presented ADME prediction of all compounds.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 10","pages":"Pages 1909-1922"},"PeriodicalIF":2.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this study, new low-toxicity tetrazole-based Schiff bases and their Pt(II) complexes were synthesized. The cytotoxicity profiles of the ligands and their Pt(II) complexes were evaluated using the WST-1 proliferation assay in healthy (Human umbilical vein endothelial cells [HUVEC]) and cancerous (Human lung adenocarcinoma, A549, and Human cervical carcinoma [HeLa]) cell lines, with cisplatin used as a reference drug. While the ligands exhibited negligible cytotoxicity, the Pt(II) complexes demonstrated moderate cytotoxic effects, with [Pt(Tet-SalCl)] showing higher potency than [Pt(Tet-SalH)]. To investigate the mechanism of cytotoxicity, in vitro calf thymus DNA (Ct-DNA) interaction studies and in silico molecular docking analyses were conducted. As a preliminary toxicity profiling step, in silico LD50 predictions were performed, yielding values of 747.416 mg/kg for (Tet-SalH) and 940.3818 mg/kg for (Tet-SalCl), supporting the low-toxicity profile of the synthesized ligands. Overall, this work presents the synthesis, characterization, and cytotoxic evaluation of novel low-toxicity ligands and their Pt(II) complexes, which, while showing slightly different activity and DNA interaction profiles compared to cisplatin at equivalent concentrations, demonstrate comparable behavior and underscore their promising therapeutic potential.
{"title":"DNA Binding and Anticancer Activity of Tetrazole-Based Schiff Bases and Their Platinum (II) Complexes via In Vitro and In Silico Endpoints","authors":"Fatma Okuş (Conceptualization Data curation Investigation Software Writing – original draft) , Nurşen Sarı (Conceptualization Formal analysis Investigation Methodology Writing – original draft Writing – review & editing) , Yaprak Dilber Simay Demir (Investigation Methodology) , Elvan Hasanoğlu Özkan (Investigation Methodology) , Fatma Ünal (Writing – review & editing) , Deniz Yüzbaşıoğlu (Project administration Supervision Writing – review & editing) , Gonca Çakmak (Conceptualization Formal analysis Investigation Methodology Supervision Writing – review & editing)","doi":"10.1080/10406638.2025.2564767","DOIUrl":"10.1080/10406638.2025.2564767","url":null,"abstract":"<div><div>In this study, new low-toxicity tetrazole-based Schiff bases and their Pt(II) complexes were synthesized. The cytotoxicity profiles of the ligands and their Pt(II) complexes were evaluated using the WST-1 proliferation assay in healthy (Human umbilical vein endothelial cells [HUVEC]) and cancerous (Human lung adenocarcinoma, A549, and Human cervical carcinoma [HeLa]) cell lines, with cisplatin used as a reference drug. While the ligands exhibited negligible cytotoxicity, the Pt(II) complexes demonstrated moderate cytotoxic effects, with [Pt(Tet-SalCl)] showing higher potency than [Pt(Tet-SalH)]. To investigate the mechanism of cytotoxicity, <em>in vitro calf thymus</em> DNA (<em>Ct</em>-DNA) interaction studies and <em>in silico</em> molecular docking analyses were conducted. As a preliminary toxicity profiling step, <em>in silico LD<sub>50</sub></em> predictions were performed, yielding values of 747.416 mg/kg for (Tet-SalH) and 940.3818 mg/kg for (Tet-SalCl), supporting the low-toxicity profile of the synthesized ligands. Overall, this work presents the synthesis, characterization, and cytotoxic evaluation of novel low-toxicity ligands and their Pt(II) complexes, which, while showing slightly different activity and DNA interaction profiles compared to cisplatin at equivalent concentrations, demonstrate comparable behavior and underscore their promising therapeutic potential.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 10","pages":"Pages 2022-2043"},"PeriodicalIF":2.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer and antibiotic resistance offer serious obstacles in drug discovery and design, which could be addressed by the synthesis of novel heterocyclic compounds with diverse combinations. In view of this a library of new molecular hybrids that contain indazole, pyrimidine, and 1,2,3-triazole heterocycles (6a-l) were synthesized and screened for their in vitro anticancer efficacy against MCF-7, PC-3, and HeLa cancer cell lines, with results compared to those of Doxorubicin. Two molecules with 2-chloro (6d) and 4-nitro (6 g) substituents presented potent activity against the PC-3 cell line, with IC50 values of 3.28 ± 0.07 µM and 3.25 ± 0.06 µM, respectively, with reference to Doxorubicin (IC50 = 3.79 ± 0.02 µM). Another molecule with 3-fluoro (6i) substituent displayed substantial action against the MCF-7 cell line, with an IC50 value of 3.26 ± 0.04 µM. The 4-nitro compound (6 g) exhibited the outstanding activity, with an IC50 value of 3.25 ± 0.07 µM against the HeLa cell line. A diverse selection of bacterial and fungal strains were employed to assess the antimicrobial potential of these compounds, and against the strains 6d, 6 g, 6h, 6i, and 6 l exhibited notably robust action. Molecular docking experiments were conducted to further investigate the binding interactions of these derivatives, compound 6 l scored highest binding affinity value of −10.4 kcal/mol.a The predicted pharmacokinetics of the molecules indicate favorable drug-likeness properties.
{"title":"Design, Synthesis, Anticancer and Antimicrobial Evaluation and In Silico Study of Indazole – Pyrimidine – 1,2,3-Triazole Hybrids","authors":"Sharada Etnoori (Investigation Methodology) , Vishnu Thumma (Conceptualization Software Visualization Writing – original draft) , Nagendra Babu Chilakala (Formal analysis) , Raju Barothu (Formal analysis) , Premalatha Kokku (Conceptualization Investigation Methodology Supervision Validation Writing – original draft Writing – review & editing)","doi":"10.1080/10406638.2025.2532069","DOIUrl":"10.1080/10406638.2025.2532069","url":null,"abstract":"<div><div>Cancer and antibiotic resistance offer serious obstacles in drug discovery and design, which could be addressed by the synthesis of novel heterocyclic compounds with diverse combinations. In view of this a library of new molecular hybrids that contain indazole, pyrimidine, and 1,2,3-triazole heterocycles (<strong>6a-l</strong>) were synthesized and screened for their <em>in vitro</em> anticancer efficacy against MCF-7, PC-3, and HeLa cancer cell lines, with results compared to those of Doxorubicin. Two molecules with 2-chloro (<strong>6d</strong>) and 4-nitro (<strong>6 g</strong>) substituents presented potent activity against the PC-3 cell line, with IC<sub>50</sub> values of <strong>3.28 ± 0.07 µM</strong> and <strong>3.25 ± 0.06 µM</strong>, respectively, with reference to Doxorubicin (IC<sub>50</sub> = <strong>3.79 ± 0.02 µM</strong>). Another molecule with 3-fluoro (<strong>6i</strong>) substituent displayed substantial action against the MCF-7 cell line, with an IC<sub>50</sub> value of <strong>3.26 ± 0.04 µM</strong>. The 4-nitro compound (<strong>6 g</strong>) exhibited the outstanding activity, with an IC<sub>50</sub> value of <strong>3.25 ± 0.07 µM</strong> against the HeLa cell line. A diverse selection of bacterial and fungal strains were employed to assess the antimicrobial potential of these compounds, and against the strains <strong>6d</strong>, <strong>6 g</strong>, <strong>6h</strong>, <strong>6i</strong>, and <strong>6 l</strong> exhibited notably robust action. Molecular docking experiments were conducted to further investigate the binding interactions of these derivatives, compound <strong>6 l</strong> scored highest binding affinity value of −10.4 kcal/mol.a The predicted pharmacokinetics of the molecules indicate favorable drug-likeness properties.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 10","pages":"Pages 1890-1908"},"PeriodicalIF":2.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1080/10406638.2025.2554206
Asma Khalaf Alshamari (Conceptualization Methodology Writing – original draft) , Ahmed A. Al Otaibi (Data curation Visualization) , Faiza I. A. Abdella (Formal analysis Writing – review & editing) , Mona Zaheed Alshammari (Data curation Software Writing – original draft) , Tamer El Malah (Conceptualization Formal analysis Investigation Methodology Resources Software Writing – original draft Writing – review & editing)
In this study, a novel series of 2,6-bis(1-aryl-1,2,3-triazol-4-yl)pyridine (BTP) derivatives (11–19) was synthesized via Cu(I)-catalyzed azide–alkyne cycloaddition. Their cytotoxic activities were evaluated against HCT-116, HepG2, and MCF-7 cancer cell lines, as well as the normal BJ-1 line, using the LDH assay. Among them, compound BTP-15 exhibited potent and selective cytotoxicity toward breast and colon cancer cells, outperforming the reference drug, while compounds 16, 11, 12, 18, 19, and 14 demonstrated strong activity against colon cancer. Molecular docking revealed favorable binding of the synthesized compounds to EGFR-TK (ΔG ≈ −7.5 kcal/mol), with up to four hydrogen bonds, and BTP-15 showed EGFR inhibition with an IC50 of 4.6 µM, inducing apoptosis and cell cycle arrest in MCF-7 cells. Docking and molecular dynamics simulations confirmed the stability of BTP-15 within the EGFR binding pocket. In silico pharmacokinetic and drug-likeness predictions further indicated promising absorption, distribution, metabolism, and toxicity profiles. These findings highlight BTP-15 as a promising EGFR-targeted lead compound with potential therapeutic relevance for breast and colon cancers.
{"title":"Exploration of Novel 2,6-Bis(1-Aryl-1,2,3-Triazol-4-yl)Pyridine Derivatives: Synthesis, Apoptotic Antiproliferative Evaluation, and In silico Insight as EGFR Inhibitors","authors":"Asma Khalaf Alshamari (Conceptualization Methodology Writing – original draft) , Ahmed A. Al Otaibi (Data curation Visualization) , Faiza I. A. Abdella (Formal analysis Writing – review & editing) , Mona Zaheed Alshammari (Data curation Software Writing – original draft) , Tamer El Malah (Conceptualization Formal analysis Investigation Methodology Resources Software Writing – original draft Writing – review & editing)","doi":"10.1080/10406638.2025.2554206","DOIUrl":"10.1080/10406638.2025.2554206","url":null,"abstract":"<div><div>In this study, a novel series of 2,6-bis(1-aryl-1,2,3-triazol-4-yl)pyridine (BTP) derivatives (<strong>11–19</strong>) was synthesized <em>via</em> Cu(I)-catalyzed azide–alkyne cycloaddition. Their cytotoxic activities were evaluated against HCT-116, HepG2, and MCF-7 cancer cell lines, as well as the normal BJ-1 line, using the LDH assay. Among them, compound BTP-15 exhibited potent and selective cytotoxicity toward breast and colon cancer cells, outperforming the reference drug, while compounds <strong>16</strong>, <strong>11</strong>, <strong>12</strong>, <strong>18</strong>, <strong>19</strong>, and <strong>14</strong> demonstrated strong activity against colon cancer. Molecular docking revealed favorable binding of the synthesized compounds to EGFR-TK (ΔG ≈ −7.5 kcal/mol), with up to four hydrogen bonds, and BTP-<strong>15</strong> showed EGFR inhibition with an IC<sub>50</sub> of 4.6 µM, inducing apoptosis and cell cycle arrest in MCF-7 cells. Docking and molecular dynamics simulations confirmed the stability of BTP-<strong>15</strong> within the EGFR binding pocket. <em>In silico</em> pharmacokinetic and drug-likeness predictions further indicated promising absorption, distribution, metabolism, and toxicity profiles. These findings highlight BTP-<strong>15</strong> as a promising EGFR-targeted lead compound with potential therapeutic relevance for breast and colon cancers.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 10","pages":"Pages 2112-2140"},"PeriodicalIF":2.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1080/10406638.2025.2559795
Saritha Keerthi (Investigation) , Nagaraju Kerru (Supervision) , Gadhave Omkar Ganpat (Project administration) , Renjith Thomas (Software) , Suresh Maddila (Writing – original draft) , Lalu Venigalla (Resources) , Gaber A. M. Mersal (Validation) , Mohamed M. Ibrahim (Writing – review & editing)
This study designed and synthesized novel pyrazole-linked 1,3,4-oxadiazole hybrids as potent anti-tubercular agents against Mycobacterium tuberculosis (Mtb) H37Rv. These hybrids represent a promising new class of anti-tubercular agents, as demonstrated by the exceptional in vitro activity of compounds 6d and 6i (MIC = 1.56 µg/mL), which show potency equivalent to the standard drug ethambutol. The in silico molecular docking studies provide compelling evidence for their mechanism of action, revealing strong binding affinities (−6.14 to −6.25 kcal/mol) with the 4kw5 target protein through key interactions with Tyr297 and Phe362 residues. Further, this study presents a clearer distinction between the experimental (in vitro) and computational (in silico) results while maintaining their interconnected relevance. The structure–activity relationship (SAR) analysis is concisely explained, highlighting how electron-donating para-substituents (-OH, -NH2) significantly enhance anti-tubercular activity compared to electron-withdrawing groups. This dual experimental and computational validation strengthens the hybrids’ potential as lead compounds for future anti-TB drug development. The improved clarity and focus ensure readers immediately grasp both the therapeutic importance of these hybrids and the robust scientific methodology supporting their discovery.
{"title":"Design Strategy and Synthesis of Novel Pyrazole-Linked 1,3,4-Oxadiazole Hybrids as Potent Anti-Tubercular Agents","authors":"Saritha Keerthi (Investigation) , Nagaraju Kerru (Supervision) , Gadhave Omkar Ganpat (Project administration) , Renjith Thomas (Software) , Suresh Maddila (Writing – original draft) , Lalu Venigalla (Resources) , Gaber A. M. Mersal (Validation) , Mohamed M. Ibrahim (Writing – review & editing)","doi":"10.1080/10406638.2025.2559795","DOIUrl":"10.1080/10406638.2025.2559795","url":null,"abstract":"<div><div>This study designed and synthesized novel pyrazole-linked 1,3,4-oxadiazole hybrids as potent anti-tubercular agents against <em>Mycobacterium tuberculosis</em> (Mtb) H37Rv. These hybrids represent a promising new class of anti-tubercular agents, as demonstrated by the exceptional <em>in vitro</em> activity of compounds <strong>6d</strong> and <strong>6i</strong> (MIC = 1.56 µg/mL), which show potency equivalent to the standard drug ethambutol. The <em>in silico</em> molecular docking studies provide compelling evidence for their mechanism of action, revealing strong binding affinities (−6.14 to −6.25 kcal/mol) with the 4kw5 target protein through key interactions with Tyr297 and Phe362 residues. Further, this study presents a clearer distinction between the experimental (<em>in vitro</em>) and computational (<em>in silico</em>) results while maintaining their interconnected relevance. The structure–activity relationship (SAR) analysis is concisely explained, highlighting how electron-donating para-substituents (-OH, -NH<sub>2</sub>) significantly enhance anti-tubercular activity compared to electron-withdrawing groups. This dual experimental and computational validation strengthens the hybrids’ potential as lead compounds for future anti-TB drug development. The improved clarity and focus ensure readers immediately grasp both the therapeutic importance of these hybrids and the robust scientific methodology supporting their discovery.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 10","pages":"Pages 2141-2151"},"PeriodicalIF":2.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1080/10406638.2025.2562259
Ahmet Bugra Aksel (Data curation Methodology Writing – original draft) , Mahmut Gozelle (Formal analysis Methodology) , Filiz Bakar-Ates (Methodology) , Yesim Ozkan (Methodology) , Erva Ozkan (Methodology) , Gokcen Eren (Conceptualization Methodology Project administration Resources Supervision Writing – original draft Writing – review & editing)
As a key member of the human sirtuin family, Sirtuin 2 (SIRT2) is crucial in orchestrating numerous biological processes, such as cell cycle regulation, apoptosis, and metabolic homeostasis, and has emerged as a promising biomarker for various conditions, particularly neurodegenerative diseases, and cancer. Given the growing therapeutic interest focused toward SIRT2 inhibition, we have synthesized a series of 1,3,4-oxadiazole/thiadiazole-2-arylthioacetamides featuring 2-/3-substituted benzyl or pyrimidin-2-ylmethyl at the 5th position of the oxadiazole/thiadiazole ring, to evaluate their potential as SIRT2 inhibitors. Among the compounds synthesized, ST95 displayed selective inhibitory activity against SIRT2 with an IC50 value of 10.62 µM and inhibited the growth of MCF-7 (IC50 = 111.10 µM) and LNCaP (IC50 = 14.69 µM) cancer cell lines, highlighting its potential as a lead compound for further development.
{"title":"Targeting SIRT2 with Oxadiazole/Thiadiazole-Based Acetamides: In Silico Screening and In Vitro Cytotoxicity Evaluation","authors":"Ahmet Bugra Aksel (Data curation Methodology Writing – original draft) , Mahmut Gozelle (Formal analysis Methodology) , Filiz Bakar-Ates (Methodology) , Yesim Ozkan (Methodology) , Erva Ozkan (Methodology) , Gokcen Eren (Conceptualization Methodology Project administration Resources Supervision Writing – original draft Writing – review & editing)","doi":"10.1080/10406638.2025.2562259","DOIUrl":"10.1080/10406638.2025.2562259","url":null,"abstract":"<div><div>As a key member of the human sirtuin family, Sirtuin 2 (SIRT2) is crucial in orchestrating numerous biological processes, such as cell cycle regulation, apoptosis, and metabolic homeostasis, and has emerged as a promising biomarker for various conditions, particularly neurodegenerative diseases, and cancer. Given the growing therapeutic interest focused toward SIRT2 inhibition, we have synthesized a series of 1,3,4-oxadiazole/thiadiazole-2-arylthioacetamides featuring 2-/3-substituted benzyl or pyrimidin-2-ylmethyl at the 5th position of the oxadiazole/thiadiazole ring, to evaluate their potential as SIRT2 inhibitors. Among the compounds synthesized, <strong>ST95</strong> displayed selective inhibitory activity against SIRT2 with an IC<sub>50</sub> value of 10.62 µM and inhibited the growth of MCF-7 (IC<sub>50</sub> = 111.10 µM) and LNCaP (IC<sub>50</sub> = 14.69 µM) cancer cell lines, highlighting its potential as a lead compound for further development.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 10","pages":"Pages 2064-2086"},"PeriodicalIF":2.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1080/10406638.2025.2498637
Asma Khalaf Alshamari , Faiza I. A. Abdella , Aljazi Abdullah AlRashidi , Nuha Othman S. Alsaif , Hissah Khashman Alshammari , Mona Zaheed Alshammari , Tamer El Malah
A series of heterocyclic naphthalene-1,2,3-triazole derivatives (12–21) were synthesized via a click reaction, resulting in high yields (83–93%). The cytotoxic effects of these derivatives were investigated on HCT-116, HePG-2, and MCF-7 cancer cell lines. Compound 20 exhibited the greatest level of activity against the tested cell lines, showing significant selectivity for tumor cells. Treatment with compound 20 on breast cancer cells led to increased early and late apoptosis, necrosis, and enhanced cell aggregation during the G2/M phase, resulting in a 36.18% cellular percentage. Compound 20 also displayed significant EGFR inhibitory activity, comparable to erlotinib’s IC50, suggesting its potential for developing new breast cancer treatments. Molecular docking revealed a specific interaction between compound 20 and the binding pocket of EGFR. These results indicate that compound 20 could be a promising candidate for further development in cancer therapy.
{"title":"Targeting EGFR Kinase Inhibitor by Novel Naphthalene-1,2,3-Triazole Hybrids via Click Chemistry: Synthesis, Cell-Cycle Arrest, Apoptosis, and In Silico Studies","authors":"Asma Khalaf Alshamari , Faiza I. A. Abdella , Aljazi Abdullah AlRashidi , Nuha Othman S. Alsaif , Hissah Khashman Alshammari , Mona Zaheed Alshammari , Tamer El Malah","doi":"10.1080/10406638.2025.2498637","DOIUrl":"10.1080/10406638.2025.2498637","url":null,"abstract":"<div><div>A series of heterocyclic naphthalene-1,2,3-triazole derivatives (<strong>12–21)</strong> were synthesized <em>via</em> a click reaction, resulting in high yields (83–93%). The cytotoxic effects of these derivatives were investigated on HCT-116, HePG-2, and MCF-7 cancer cell lines. Compound <strong>20</strong> exhibited the greatest level of activity against the tested cell lines, showing significant selectivity for tumor cells. Treatment with compound <strong>20</strong> on breast cancer cells led to increased early and late apoptosis, necrosis, and enhanced cell aggregation during the G2/M phase, resulting in a 36.18% cellular percentage. Compound <strong>20</strong> also displayed significant EGFR inhibitory activity, comparable to erlotinib’s IC<sub>50</sub>, suggesting its potential for developing new breast cancer treatments. Molecular docking revealed a specific interaction between compound <strong>20</strong> and the binding pocket of EGFR. These results indicate that compound <strong>20</strong> could be a promising candidate for further development in cancer therapy.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 10","pages":"Pages 1944-1967"},"PeriodicalIF":2.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this study, we have described the preparation of substituted dehydroaripiprazoles 7a–h from readily available 3-chloroaniline under mild reaction conditions. They were designed specific structural modifications of aripiprazole. Furthermore, the compounds illustrated as potent in vitro inhibitors of anti-cancer activity. Among these compounds, 7a and 7g were found to be the most active ones with a MIC of 1.58 μg/mL and 3.12 μg/mL, respectively. Moreover, in vitro findings were supported by molecular docking studies with the known anti-TB target. The molecular docking studies on 7a and 7g hit compounds clearly validated hydrogen bonds interactions with the enoyl-acp reductase (INHA). From these results, we indicate that these classes of compounds may give future development, and probably get drug alternative for anti-cancer treatment.
{"title":"Design an Efficient Synthesis Method of Dehydroaripiprazole Analogs and the Preliminary Study of Their in Vitro Antituberculosis Activity","authors":"Appalanaidu Satipidakala , Atchutarao Pathigoolla , Ramakrishna Rao Bhonsle , Ramana Tamminana","doi":"10.1080/10406638.2025.2503772","DOIUrl":"10.1080/10406638.2025.2503772","url":null,"abstract":"<div><div>In this study, we have described the preparation of substituted dehydroaripiprazoles <strong>7a–h</strong> from readily available 3-chloroaniline under mild reaction conditions. They were designed specific structural modifications of aripiprazole. Furthermore, the compounds illustrated as potent <em>in vitro</em> inhibitors of anti-cancer activity. Among these compounds, <strong>7a</strong> and <strong>7g</strong> were found to be the most active ones with a MIC of 1.58 μg/mL and 3.12 μg/mL, respectively. Moreover, <em>in vitro</em> findings were supported by molecular docking studies with the known anti-TB target. The molecular docking studies on <strong>7a</strong> and <strong>7g</strong> hit compounds clearly validated hydrogen bonds interactions with the enoyl-acp reductase (INHA). From these results, we indicate that these classes of compounds may give future development, and probably get drug alternative for anti-cancer treatment.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 10","pages":"Pages 1875-1889"},"PeriodicalIF":2.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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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