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}
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}
Pub Date : 2025-11-26Epub Date: 2025-09-08DOI: 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 : 2025-11-26Epub Date: 2025-09-17DOI: 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 : 2025-11-26Epub Date: 2025-05-13DOI: 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}
Pub Date : 2025-11-26Epub Date: 2025-09-23DOI: 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}
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}
A highly efficient and environmentally friendly synthetic strategy has been developed for the construction of novel bis(trifluoromethyl)phenyl-quinoline-benzamide-[1, 8]-naphthyridine and imidazo[1,2-a][1, 8]-naphthyridine derivatives. The structures of the synthesized compounds were confirmed by 1HNMR,13CNMR, and Mass data. The synthesized compounds (5/7a-e) were evaluated for their anticancer activity against three human cancer cell lines: MCF-7, A549, and SiHa. Among them, derivatives 5b and 5e displayed the most potent activity with IC50 values 11.25 ± 0.09 μM, 23.19 ± 0.45 μM, 29.22 ± 0.35 μM and 13.45 ± 0.09 μM, 26.24 ± 0.41 μM, 30.18 ± 0.39 μM. The synthesized derivatives were evaluated for their antimicrobial activity against pathogenic bacterial and fungal strains. All synthesized compounds demonstrated notable biological activity. Molecular docking studies were performed to evaluate the interactions of compounds 5/7a–e with selected target proteins. The results revealed strong binding affinities and favorable molecular interactions, supporting their potential as therapeutic agents. These derivatives exhibited significant antimicrobial and anticancer properties. Structure–activity relationship (SAR) analysis indicated that the presence of electron-withdrawing groups and hydrogen bond donors substantially enhanced cytotoxic effects.
{"title":"Synthesis, Biological Evaluation, and Molecular Docking Studies of [1, 8]-Naphthyridine Derivatives as Potential Anticancer and Antimicrobial Agents","authors":"Sontireddy Surender Reddy (Formal analysis Methodology Writing – original draft) , Kavati Shireesha (Validation) , Kumara Swamy Jella (Supervision)","doi":"10.1080/10406638.2025.2550361","DOIUrl":"10.1080/10406638.2025.2550361","url":null,"abstract":"<div><div>A highly efficient and environmentally friendly synthetic strategy has been developed for the construction of novel bis(trifluoromethyl)phenyl-quinoline-benzamide-[1, 8]-naphthyridine and imidazo[1,2-a][1, 8]-naphthyridine derivatives. The structures of the synthesized compounds were confirmed by <sup>1</sup>HNMR,<sup>13</sup>CNMR, and Mass data. The synthesized compounds (<strong>5/7a-e)</strong> were evaluated for their anticancer activity against three human cancer cell lines: MCF-7, A549, and SiHa. Among them, derivatives <strong>5b</strong> and <strong>5e</strong> displayed the most potent activity with IC<sub>50</sub> values 11.25 ± 0.09 μM, 23.19 ± 0.45 μM, 29.22 ± 0.35 μM and 13.45 ± 0.09 μM, 26.24 ± 0.41 μM, 30.18 ± 0.39 μM. The synthesized derivatives were evaluated for their antimicrobial activity against pathogenic bacterial and fungal strains. All synthesized compounds demonstrated notable biological activity. Molecular docking studies were performed to evaluate the interactions of compounds 5/7a–e with selected target proteins. The results revealed strong binding affinities and favorable molecular interactions, supporting their potential as therapeutic agents. These derivatives exhibited significant antimicrobial and anticancer properties. Structure–activity relationship (SAR) analysis indicated that the presence of electron-withdrawing groups and hydrogen bond donors substantially enhanced cytotoxic effects.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 10","pages":"Pages 1988-2001"},"PeriodicalIF":2.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645928","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}
The development of targeted catalysts for environmental applications in the synthesis of biological compounds can be incredibly important. In the last few years, many catalysts have been reported that are potentially developable at the current time. In this research, Fe-based MOF as a bed and thiourea functionalities were constructed on it via a post-modification method. This method introduced the MOF(Fe)-TUR catalyst with hydrogen bonding ability, which selectively catalyzes the synthesis of new nicotinonitriles as well as chromeno[4,3-b]pyridine derivatives with good yields (70%–85%), suitable temperature (100 °C), easy purification and easy catalyst separation. The last step of the reaction process occurred via a cooperative vinylogous anomeric based oxidation. The structure of MOF(Fe)-TUR as a new H-bond catalyst was confirmed using several techniques such as FT-IR, XRD, XPS, SEM, EDX, Elemental mapping, BET, and BJH. The structure of the synthesized products was evaluated and confirmed by melting point, FT-IR, 1H-NMR, and 13C-NMR techniques. The novelty of this work lies in the development of a green and mild synthetic route and making MOF(Fe)-TUR as an environmentally friendly catalyst. Additionally, recycle and reusability of the presented catalyst are other advantages of the described methodology.
{"title":"Synthesis and Application of MOF(Fe)-TUR as a New H-Bond Catalyst for Synthesis of New Nicotinonitriles and Chromeno[4,3-b] Pyridines","authors":"Mahrokh Farrokh (Investigation Methodology Validation) , Hassan Sepehrmansourie (Investigation Writing – original draft) , Elham Tavakoli (Investigation Methodology Validation) , Mohammad Ali Zolfigol (Conceptualization Funding acquisition Project administration Resources Supervision Writing – review & editing) , Maryam Hajjami (Conceptualization Funding acquisition Project administration Resources Supervision Writing – review & editing)","doi":"10.1080/10406638.2025.2547604","DOIUrl":"10.1080/10406638.2025.2547604","url":null,"abstract":"<div><div>The development of targeted catalysts for environmental applications in the synthesis of biological compounds can be incredibly important. In the last few years, many catalysts have been reported that are potentially developable at the current time. In this research, Fe-based MOF as a bed and thiourea functionalities were constructed on it <em>via</em> a post-modification method. This method introduced the MOF(Fe)-TUR catalyst with hydrogen bonding ability, which selectively catalyzes the synthesis of new nicotinonitriles as well as chromeno[4,3-<em>b</em>]pyridine derivatives with good yields (70%–85%), suitable temperature (100 °C), easy purification and easy catalyst separation. The last step of the reaction process occurred <em>via</em> a cooperative vinylogous anomeric based oxidation. The structure of MOF(Fe)-TUR as a new H-bond catalyst was confirmed using several techniques such as FT-IR, XRD, XPS, SEM, EDX, Elemental mapping, BET, and BJH. The structure of the synthesized products was evaluated and confirmed by melting point, FT-IR, <sup>1</sup>H-NMR, and <sup>13</sup>C-NMR techniques. The novelty of this work lies in the development of a green and mild synthetic route and making MOF(Fe)-TUR as an environmentally friendly catalyst. Additionally, recycle and reusability of the presented catalyst are other advantages of the described methodology.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 10","pages":"Pages 1968-1987"},"PeriodicalIF":2.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645926","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 : 2025-11-26Epub Date: 2025-08-29DOI: 10.1080/10406638.2025.2551791
Amrina Bibi (Methodology) , Aftab Alam (Conceptualization Writing – original draft) , Tanzeela Ahmad Shah (Methodology Validation) , Burak Tüzün (Software Writing – original draft) , Imtiaz Ahmad (Formal analysis Investigation) , Muhammad Ayaz (Validation Visualization) , Sajjad Ur Rahman (Investigation Methodology) , Ahmed A. Elhenawy (Software Writing – review & editing) , Syed Adnan Ali Shah (Data curation Formal analysis) , Abdul Latif (Formal analysis Visualization) , Mumtaz Ali (Investigation Supervision) , Manzoor Ahmad (Project administration Supervision Writing – review & editing)
This study reports the synthesis, characterization by means of spectroscopic techniques (UV, FT-IR,1H-NMR,13C-NMR and mass) and enzyme inhibitory activities (acetyl and butyryl-cholinesterase) of new bis-Schiff bases derived from α-naphthalene acetic acid. Among the synthetic library, six analogues (3a, 3b, 3 g, 3e, 3i, and 3h) showed the promising dual inhibitory activity with IC50 values from (75.53 ± 0.47 to 103.60 ± 0.91 µmol/L for acetyl cholinesterase) and (71.28 ± 0.57 to 106.60 ± 1.83 µmol/L for butyrylcholinesterase), while the remaining compounds attributed good to moderate inhibitory effects. Furthermore, Gaussian calculations were performed to examine new bis-Schiff bases at the B3LYP, HF, and M062X levels, utilizing the 6-31++g(d,p) basis set. Molecular docking calculations were performed on a number of proteins, including AChE enzyme proteins (PDB ID: 4M0E, 1OCE, and 1QTI), and BuChE enzyme proteins (PDB ID: 5NN0, 1XLU, and 6QAE). To examine the effects and responses of these drugs on human metabolism, ADME/T calculations are conducted. MD simulations highlighted 3i-4M0E complex as top candidates, with stable 3i-4M0E complexes suggesting functional relevance. These findings underscore the potential of these compounds as leads for optimizing acetylcholinesterase inhibitors in neurological disorder therapeutics.
{"title":"Synthesis of α-Naphthalene Acetic Acid Derived Bis-Schiff Bases: In Vitro Cholinesterase Inhibition, Molecular Docking, Dynamics Simulations, Kinetics, and DFT Analysis","authors":"Amrina Bibi (Methodology) , Aftab Alam (Conceptualization Writing – original draft) , Tanzeela Ahmad Shah (Methodology Validation) , Burak Tüzün (Software Writing – original draft) , Imtiaz Ahmad (Formal analysis Investigation) , Muhammad Ayaz (Validation Visualization) , Sajjad Ur Rahman (Investigation Methodology) , Ahmed A. Elhenawy (Software Writing – review & editing) , Syed Adnan Ali Shah (Data curation Formal analysis) , Abdul Latif (Formal analysis Visualization) , Mumtaz Ali (Investigation Supervision) , Manzoor Ahmad (Project administration Supervision Writing – review & editing)","doi":"10.1080/10406638.2025.2551791","DOIUrl":"10.1080/10406638.2025.2551791","url":null,"abstract":"<div><div>This study reports the synthesis, characterization by means of spectroscopic techniques (UV, FT-IR,<sup>1</sup>H-NMR,<sup>13</sup>C-NMR and mass) and enzyme inhibitory activities (acetyl and butyryl-cholinesterase) of new <em>bis</em>-Schiff bases derived from α-naphthalene acetic acid. Among the synthetic library, six analogues <strong>(3a, 3b, 3 g, 3e, 3i,</strong> and <strong>3h)</strong> showed the promising dual inhibitory activity with IC<sub>50</sub> values from (75.53 ± 0.47 to 103.60 ± 0.91 µmol/L for acetyl cholinesterase) and (71.28 ± 0.57 to 106.60 ± 1.83 µmol/L for butyrylcholinesterase), while the remaining compounds attributed good to moderate inhibitory effects. Furthermore, Gaussian calculations were performed to examine new <em>bis</em>-Schiff bases at the B3LYP, HF, and M062X levels, utilizing the 6-31++g(d,p) basis set. Molecular docking calculations were performed on a number of proteins, including AChE enzyme proteins (PDB ID: 4M0E, 1OCE, and 1QTI), and BuChE enzyme proteins (PDB ID: 5NN0, 1XLU, and 6QAE). To examine the effects and responses of these drugs on human metabolism, ADME/T calculations are conducted. MD simulations highlighted <strong>3i</strong>-4M0E complex as top candidates, with stable <strong>3i</strong>-4M0E complexes suggesting functional relevance. These findings underscore the potential of these compounds as leads for optimizing acetylcholinesterase inhibitors in neurological disorder therapeutics.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"45 10","pages":"Pages 2087-2111"},"PeriodicalIF":2.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645480","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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