Polycyclic Aromatic Compounds最新文献

{"title":"Synthesis, Antioxidant and Anti-proliferative Activity of Novel Pyridonaphthyridines: Multicomponent Reactions of Electron Deficient Acetylenic Compounds","authors":"Somayeh Soleimani Amiri (Formal analysis Writing – original draft Writing – review & editing) ,&nbsp;Zahra Azizi (Formal analysis Software Writing – original draft Writing – review & editing) ,&nbsp;Mehdi Ghambarian (Investigation Software Writing – original draft Writing – review & editing) ,&nbsp;Zinatossadat Hossaini (Investigation Writing – original draft Writing – review & editing)","doi":"10.1080/10406638.2025.2604549","DOIUrl":"10.1080/10406638.2025.2604549","url":null,"abstract":"<div><div>In this investigation, we successfully synthesized fused pyridonaphthyridines, a newly identified class of fused heterocyclic compounds, through an efficient multicomponent reaction. The methodology involved utilizing 3-(2-hydroxyphenyl)-3-iminopropanamide, 2-(1,3-diimino-1,3-dihydro-2H-inden-2-ylidene) malononitrile, alkyl bromides, and activated acetylenic derivatives within an aqueous medium at ambient temperature. Notably, the process was facilitated by a reusable catalyst composed of Ag/Fe₃O₄@GO. The newly synthesized compounds were subsequently evaluated for their antiproliferative potential against MCF-7 breast cancer and HCT-15 colon cancer cell lines using the Sulfo-rhodamine B (SRB) assay, along with their antioxidant capabilities. Among the compounds tested, derivatives <strong>5c</strong> and <strong>5 g</strong> demonstrated notably superior antiproliferative activity relative to their counterparts. To further explore their interaction with biological macromolecules, these two compounds underwent UV-Vis spectral analysis to determine their binding affinities to DNA and bovine serum albumin (BSA). The results revealed affinity constants of K5c-DNA = 7.32 × 10³ M⁻¹, K5g-DNA = 2.09 × 10⁴ M⁻¹, K5c-BSA = 5.32 × 10⁴ M⁻¹, and K5g-BSA = 8.24 × 10⁴ M⁻¹, respectively. The outcomes of this study could provide novel insights into the relationship between the chemical structure of these pyridonaphthyridine analogs and their capacity to inhibit cancer cell proliferation.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"46 3","pages":"Pages 390-410"},"PeriodicalIF":2.6,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147807225","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}

{"title":"Synthesis, Cytotoxicity, and Molecular Modeling of Novel Benzamide-Derived Hydrazone Derivatives as ALDOA Inhibitors in Colorectal Cancer","authors":"Sevil Şenkardeş (Conceptualization Data curation Investigation Project administration Supervision Validation Writing – original draft Writing – review & editing) ,&nbsp;Gökçe Patlak (Formal analysis Funding acquisition Investigation Methodology Validation Writing – original draft Writing – review & editing) ,&nbsp;Edanur Çolak (Formal analysis Investigation Visualization Writing – original draft Writing – review & editing) ,&nbsp;Bensu Kozan (Investigation Methodology Software Visualization Writing – original draft) ,&nbsp;Özge Çevik (Investigation Project administration Supervision Writing – original draft Writing – review & editing) ,&nbsp;Sevgi Karakuş (Conceptualization Data curation Funding acquisition Project administration Resources Writing – original draft Writing – review & editing) ,&nbsp;Faika Başoğlu (Methodology Resources Software Validation Visualization Writing – original draft Writing – review & editing)","doi":"10.1080/10406638.2025.2611826","DOIUrl":"10.1080/10406638.2025.2611826","url":null,"abstract":"<div><div>Colorectal cancer remains a major global health challenge, underscoring the need for new therapeutic agents targeting cancer metabolism. In this study, a novel series of benzamide-derived hydrazone derivatives <strong>(3a–i)</strong> was designed and synthesized as the potential Aldolase A (ALDOA) inhibitors. Their antiproliferative activity was first evaluated against HT-29 human colorectal cancer cells and L929 mouse fibroblast cells. Among the series, compounds <strong>3a</strong> (5-bromo-2-methoxyphenyl) and <strong>3d</strong> (5-nitrofuran-2-yl) displayed particularly potent and selective cytotoxicity, with IC₅₀ values of 0.382 ± 0.115 µM and 0.101 ± 0.066 µM, respectively. Both compounds also effectively inhibited ALDOA (72.06 ± 4.12% and 82.09 ± 7.14%, respectively, at 10 µM), reduced lactate production, downregulated hypoxia-inducible factor-1α (HIF-1α), and induced apoptosis, demonstrating a strong metabolic inhibition profile. Furthermore, 300 ns molecular dynamics simulations of the compound <strong>3d</strong>–ALDOA complex revealed a stable and specific binding mode with the persistent intermolecular interactions, supporting its experimentally observed inhibitory potential. Collectively, these findings introduce a new hydrazone-based scaffold with enhanced potency and selectivity, representing a promising lead for further development in colorectal cancer therapy.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"46 3","pages":"Pages 357-368"},"PeriodicalIF":2.6,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147807231","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}

{"title":"Novel Pyrido[2,3-d]Pyrimidine Derivatives: Synthesis, In Silico and Cytotoxic Evaluation and Identification of a Potential Anticancer Agent","authors":"Hossein Garmabi (Data curation Writing – original draft) ,&nbsp;Maryam M. Matin (Conceptualization Supervision Formal analysis Writing – review & editing) ,&nbsp;Hossein Sabet-Sarvestani (Investigation Supervision) ,&nbsp;Hossein Eshghi (Investigation Supervision)","doi":"10.1080/10406638.2025.2611794","DOIUrl":"10.1080/10406638.2025.2611794","url":null,"abstract":"<div><div>In this study, the main objective was to develop new pyrido[2,3-<em>d</em>]pyrimidine derivatives with improved anticancer activity. To achieve this, a novel series of pyrido[2,3-<em>d</em>]pyrimidine derivatives was synthesized and evaluated for their anticancer potential using both computational and experimental approaches. Molecular docking was performed to assess their binding affinity toward epidermal growth factor receptor, a protein overexpressed in prostate cancer. ADMET analyses were conducted to predict pharmacokinetic and toxicity profiles, which revealed overall favorable results. Based on the docking outcomes, five compounds with the highest binding affinities were selected for further biological evaluation. The cytotoxicity of these compounds was tested against PC-3 prostate cancer cells. Among them, compound <strong>8e</strong> exhibited the most potent cytotoxic activity, with IC₅₀ values of 35.60 ± 1.14, 14.02 ± 1.26, and 9.39 ± 1.23 µM after 24, 48, and 72 h of treatment, respectively, compared with doxorubicin (IC₅₀ ≈ 2 μM). The selectivity index (SI) of <strong>8e</strong> against normal HDF cells was 1.23, 2.54, and 5.72 at the corresponding time points. Flow cytometry analysis revealed that compound <strong>8e</strong> induced cell cycle arrest at the S phase, while apoptosis assay showed a significant increase in total apoptotic cells—from 5.78% in untreated cells to 44.78% after treatment. In conclusion, with strong cytotoxicity, pronounced apoptosis induction, and improved selectivity over time, compound <strong>8e</strong> may serve as a promising anticancer candidate.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"46 3","pages":"Pages 469-486"},"PeriodicalIF":2.6,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147806793","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}

{"title":"Evaluation of Geometrical, Vibrational, Electronic and Other Molecular Parameters of Two Vinyl Sulfone Derivatives Using Experimental Spectroscopic and Computational Density Functional Theory Analyses","authors":"K. Suresh (Data curation Validation) ,&nbsp;K. Srishailam (Supervision Writing – original draft) ,&nbsp;S. Radhika (Formal analysis) ,&nbsp;J. Sunil (Formal analysis Visualization) ,&nbsp;A. Balakrishna (Formal analysis Methodology Resources Software) ,&nbsp;G. Ramana Rao (Resources Software Writing – review & editing)","doi":"10.1080/10406638.2025.2611786","DOIUrl":"10.1080/10406638.2025.2611786","url":null,"abstract":"<div><div>The goal of this article is to characterize 2-(phenylsulfonyl)vinylbenzene(PVB) and 1-chloro-4-(phenylsulfonyl)vinylbenzene(CVB), using experimental spectroscopic techniques (FT-IR, FT Raman, UV-Vis) and computational tools (DFT, TD-DFT, Gauss View, MOLVIB, NBO software ORIGIN). Density functional theory formalism at DFT/B3LYP/6-311++G(d,p) level was employed to determine barrier hights around (C1-S12), (S12-C15) and (C17-C19) bonds, ground state geometry, general valence force field, harmonic vibrational fundamentals, and vital molecular electronic parameters (FMO,NLO, NBO, MESP), whereas, in combination with MOLVIB, it provided scaled values for force field and vibrational frequencies, along with eigenvectors, potential energy distribution (PED), infrared and Raman intensities, and simulated vibrational spectra, while its time dependent variant computed absorption maxima (<em>λ</em>_max) and oscillator strengths and simulated UV-Vis spectra for electron transitions in various solvents for the target molecules. Experimental and corresponding theoretical parameters for structure, and vibrational wavenumbers, and measured and simulated spectra agreed very well. Experimental and scaled vibrational frequencies agreed with rms error 9.0 and 5.4 cm⁻¹ for PVB and CVB, respectively. PED and eigenvectors helped in the assignment of all the eighty-one fundamentals of each of the two molecules unambiguously. Comparative study made for frontier molecular orbital (FMO) parameters revealed that PVB is less reactive and more stable, in comparison with CVB, with energy gap (ΔE) values 3.60 and 3.23 eV, for PVB and CVB, respectively. Nonlinear optical (NLO) investigation ascertained their utility for NLO applications. Natural bond orbital (NBO) analysis made it clear that the highest contribution of stabilization energy comes from (C3–C4)π→(C1–C2)π* interaction which were 23.40 and 23.50 kcal/mol for PVB and CVB, respectively. MESP mapping confirmed that sulfone moiety was an electrophilic group and identified its oxygen atoms as sites for an electrophilic attack. The most significant aspect of these investigations was, that we tried to explain major changes observed for vibrational and electronic parameters of CVB in terms of the increased mass, and inductive and resonance effects of the chlorine atom, in comparison with PVB, to the extent possible.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"46 3","pages":"Pages 411-439"},"PeriodicalIF":2.6,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147807226","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}

{"title":"Design, Synthesis, Biological Evaluation and In-Silico Investigation, Molecular Docking, Molecular Dynamics Simulations, and ADMET Profiling of Novel Thiazole-Based Derivatives","authors":"Ghada Emad Abd El-Ghani (Writing – original draft Writing – review & editing) ,&nbsp;Salwa Mahmoud El-Sayed (Conceptualization Investigation Methodology Writing – review & editing) ,&nbsp;Ahmed Fikry El-Sayed (Investigation Methodology) ,&nbsp;Ghada Gamal El-Bana (Investigation Writing – review & editing)","doi":"10.1080/10406638.2025.2587067","DOIUrl":"10.1080/10406638.2025.2587067","url":null,"abstract":"<div><div>In the present study, the design of 2-aminothiazole and 2-(1-phenylethylidene)hydrazine-1-carbothioamide <strong>(1)</strong> were reacted with different reagents such as α-bromocarbonyl derivatives, chloroacetone, and ethyl-2-cloroacetoacetate 1-chloro-1-(aryldiazenyl) propan-2-one, and ethyl 2-chloro-2-(aryldiazenyl) acetate to produce the corresponding thiazole products <strong>4, 5, 9a-d,</strong> <strong>10, 13a,b,</strong> and <strong>15a-h</strong>, respectively. The synthesized compounds were screened for breast cancer cell lines MCF7 and MDA-MB231 using MTT assay and doxorubicin was used as the standard drug. The biological studies showed that compounds <strong>9a, 9d, 10,</strong> and <strong>15d</strong> had notable cytotoxic activity against MCF-7 cell line. Furthermore, compound <strong>9d</strong> displayed the good cytotoxic activity against both the MCF7 and MDA-MB231 cell lines. These findings led to the synthetic chemical <strong>9d</strong> being chosen for biological research as an antioxidant and anti-breast cancer agent comparing with the standard compound. The apoptosis/necrosis assay showed significantly higher apoptosis levels in the treated samples (<strong>9d</strong>/MCF7 and <strong>9d</strong>/MDA-MB231) compared to the controls. Molecular docking was employed to examine how the most promising compounds interacted with key anticancer target proteins. The docking results showed that compounds <strong>9a, 9d, 15b, 15d,</strong> and <strong>17b</strong> displayed strong binding energies and effectively engaged with the active sites of the CDK2, ERα, EGFR, and VEGFR2 receptors. These interactions encompassed a range of molecular contacts highlighting the compounds’ potential to block enzyme activity and deliver significant anticancer effects. Additionally, the <em>silico</em>-ADMET analysis of compounds <strong>9a, 9d, 15b, 15d,</strong> and <strong>17b</strong> showed compliance with Lipinski guidelines, indicating favorable physicochemical characteristics. These compounds are expected to exhibit good oral bioavailability, and minimal toxicity risks.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"46 3","pages":"Pages 303-333"},"PeriodicalIF":2.6,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147807230","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}

{"title":"Green Synthesis of Functionalized Thiazolo[3,2-a]Pyrimidines Using Choline Chloride/Pentaerythritol as a Green Solvent: Biological Activity Evaluation","authors":"Fatemeh Kalhorzadeh (Investigation Writing – original draft) ,&nbsp;Ashraf Sadat Shahvelayati (Project administration Writing – original draft Writing – review & editing) ,&nbsp;Zahra Azizi (Software Writing – original draft) ,&nbsp;Shiva Khalil-Moghaddam (Formal analysis Methodology Writing – original draft) ,&nbsp;Zinatossadat Hossaini (Writing – original draft Writing – review & editing)","doi":"10.1080/10406638.2025.2599264","DOIUrl":"10.1080/10406638.2025.2599264","url":null,"abstract":"<div><div>A unique deep eutectic solvent solution was created by combining choline chloride with 2,2-bis(hydroxymethyl)propane-1,3-diol (pentaerythritol). In this article, we discussed the synthesis of thiazolo[3,2-a]pyrimidine which utilized environmentally friendly solvent and SiO₂/Fe₃O₄@GO as a reusable catalyst, aldehydes, ethyl acetoacetate, thiourea, and alkyl bromas at room temperature in high yields. Using a water extract from the rhizome of <em>Petasites hybridus</em> for the production of SiO₂/Fe₃O₄@GO is an environmentally acceptable production method which is also a mild base that is used into the manufacturing process. Additionally, diphenyl-picrylhydrazine (DPPH) and ferric reduction tests will be utilized in order to trap radicals in the thiazolo[3,2-a]pyrimidine that has been produced and evaluate the antioxidant characteristics of the compound of interest. The effectiveness of a wide variety of thiazolo[3,2-a]pyrimidine derivatives as antibacterial agents was evaluated by employing both Gram-positive and Gram-negative bacteria, as well as the disk diffusion method. It was determined, on the basis of the findings, that the thiazolo[3,2-a]pyrimidine that was produced was particularly effective in inhibiting the development of bacteria. Through the utilization of this robust technique, numerous enhancements can be achieved in the synthesis of novel thiazolo[3,2-a]pyrimidine. In addition to these enhancements, the reaction times have been reduced, the product yields have been improved, and the catalyst extraction from the byproducts has been simplified.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"46 3","pages":"Pages 369-389"},"PeriodicalIF":2.6,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147807232","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}

{"title":"Synthesis of New Quinazolinone-Based 1,2,3–Triazole Scaffolds as Potent Anticancer Agents: Molecular Docking and ADME Studies","authors":"Somsole Chandrasekhar (Conceptualization Data curation Methodology) ,&nbsp;Venkatathri Narayanan (Conceptualization Project administration Supervision Writing – original draft) ,&nbsp;Gutam Madhu (Data curation Formal analysis Resources) ,&nbsp;Jonnala Sandhya (Formal analysis Resources Software) ,&nbsp;Andugula Chandra Mohan (Formal analysis Resources Software) ,&nbsp;Vundyala Neeraja (Formal analysis Resources Writing – original draft) ,&nbsp;Tejeswara Rao Allaka (Conceptualization Writing – original draft Writing – review & editing)","doi":"10.1080/10406638.2026.2618267","DOIUrl":"10.1080/10406638.2026.2618267","url":null,"abstract":"<div><div>Driven by the urgent need for novel anticancer agents capable of overcoming limitations associated with conventional therapies, a new series of quinazolinone derivatives featuring 1,2,3–triazole–acetamide linkers was successfully produced through a copper(I)-catalyzed azide alkyne cycloaddition (CuAAC)-catalyzed cyclocondensation of 3-ethyl-2-(prop-2-yn-1-ylsulfonyl) quinazolin-4(3<em>H</em>)-one with the corresponding 2-azido-<em>N</em>-phenylacetamides. The structures of the synthesized compounds were confirmed through ¹H/¹³C NMR, IR, and HRMS spectroscopic techniques. The novel compounds were evaluated against human lung carcinoma (A549 and NCI-H460), human colorectal carcinoma (HT29 and HCT116), and also hepatocellular liver carcinoma (HepG-2) cell line. Among them, compound <strong>6e</strong> demonstrated potent cytotoxicity against A549 (IC₅₀ = 4.80 ± 1.04 <em>μ</em>g. mL⁻¹) and HT29 (IC₅₀ = 5.40 ± 0.94 <em>μ</em>g. mL⁻¹) cell lines, showing efficacy comparable to doxorubicin (IC₅₀ = 5.04 ± 1.15 and 5.80 ± 0.89 <em>μ</em>g. mL⁻¹, respectively). Notably, <strong>6h</strong> inhibited the liver cancer cell line HepG-2 with an IC₅₀ of 6.12 ± 0.56 <em>μ</em>g. mL⁻¹, when compared to DXN (7.12 ± 1.06 <em>μ</em>g. mL⁻¹). Additionally, the molecular modeling approach was employed to correlate the <em>in vitro</em> anticancer cell viability activity well with the <em>in silico</em> study, and the result obtained corroborated that active analogues established several key interactions at positions Arg483(A), Phe478(A), Leu484(A), Ile506(A), Thr458(A), Ser486(A), Asn485(A), and Gly527(A) with the active site of the lung cancer (PDB code: 1X2R). Extending our exploration, an analysis of the ADME-Tox profiling confirmed the safe use of these newly synthesized scaffolds, paving the way for promising therapeutic applications in the field of anticancer therapy. Collectively, these findings underscore the potential of 1,2,3-triazole hybrids, particularly compounds <strong>6e</strong> and <strong>6h</strong>, as the promising leads for the development of new anticancer agents.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"46 3","pages":"Pages 334-356"},"PeriodicalIF":2.6,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147807228","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}

{"title":"Unlocking the Potential of CDK4/6 Inhibitors: A Deep Dive into Abemaciclib, Palbociclib, and Ribociclib Succinate via DFT, Docking, Pharmacokinetics and MD Simulations","authors":"Y. Sheena Mary (Conceptualization Data curation Formal analysis Investigation Methodology Project administration Supervision Validation Visualization Writing – original draft Writing – review & editing) ,&nbsp;V. Baiju (Conceptualization Data curation Formal analysis Investigation Methodology Visualization Writing – original draft) ,&nbsp;Jamelah S. Al-Otaibi (Conceptualization Data curation Formal analysis Investigation Methodology Resources Software Supervision Visualization Writing – original draft) ,&nbsp;Maria Cristina Gamberini (Conceptualization Data curation Formal analysis Investigation Methodology Resources Visualization Writing – original draft Writing – review & editing)","doi":"10.1080/10406638.2025.2597004","DOIUrl":"10.1080/10406638.2025.2597004","url":null,"abstract":"<div><div>Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have emerged as one of the most transformative classes of targeted therapeutics in modern oncology. Despite of their clinical success, especially in hormone receptor-positive breast cancer, the molecular mechanisms driving differential patient response, acquired resistance, and off-target effects remain incompletely understood. In this work, we present a comprehensive and integrative analysis that combines molecular docking, structure-activity relationships, and mechanistic biochemical insights to unravel the key factors governing CDK4/6 inhibitor performance. By evaluating ligand binding dynamics, conformational shifts within the ATP-binding pocket, and the impact of chemical substituents on drug-protein interactions, we reveal a set of structural features that strongly correlate with potency, selectivity, and resistance propensity. Our study further highlights previously overlooked allosteric regions that may serve as next-generation design targets. Together, these findings offer a deeper molecular-level understanding of CDK4/6 inhibition and provide a roadmap for engineering more effective anticancer agents with enhanced specificity and reduced toxicity. This work aims to accelerate rational drug design efforts and support the development of superior therapeutic strategies for CDK4/6-drigen malignancies. This study provides an in-depth computational analysis of three FDA-approved CDK4/6 inhibitors - Abemaciclib (ABB), Palbociclib (PAB), and Ribociclib succinate (RIB) - using DFT, docking, MD simulations, and pharmacokinetic profiling. Structural optimization and vibrational analyses were conducted alongside FMO and MEP mapping to identify reactive sites.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"46 3","pages":"Pages 440-468"},"PeriodicalIF":2.6,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147807224","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}

{"title":"Synthesis and In Silico Studies of New Tetrahydrobenzo[b]Thiophenes and Heteroannulated Candidates as Antiproliferative Agents","authors":"Amna S. Elgubbi (Conceptualization Data curation Investigation Methodology Writing – original draft Writing – review & editing) ,&nbsp;Sayed K. Ramadan (Conceptualization Data curation Investigation Methodology Validation Visualization Writing – original draft Writing – review & editing) ,&nbsp;Sobhi M. Gomha (Software Validation Writing – review & editing) ,&nbsp;Magdi E. A. Zaki (Software Validation Writing – review & editing) ,&nbsp;Eman A. E. El-Helw (Conceptualization Investigation Methodology Writing – original draft Writing – review & editing)","doi":"10.1080/10406638.2026.2621207","DOIUrl":"10.1080/10406638.2026.2621207","url":null,"abstract":"<div><div>Cancer remains a major global health challenge, emphasizing the need for new therapeutic agents. A series of tetrahydrobenzo[<em>b</em>]thiophene derivatives was synthesized from a <em>β</em>-enaminonitrile precursor and designed to target tubulin, a key protein in mitosis. The purity of compounds obtained was checked and confirmed with HPLC analysis. Antiproliferative activity was assessed against MCF-7 (breast) and HepG2 (liver) cancer cell lines, and cytotoxicity against the non-cancerous WI-38 cell line identified <em>N</em>-phenylamino- and <em>N</em>-benzyl-tetrahydrobenzo[<em>b</em>]thienopyrimidines as the most potent, likely due to their hydrophobic nature. The selectivity index showed the more selective toxicity of these derivatives toward cancer cells rather than normal cells. Molecular docking revealed strong binding affinities and favorable interactions to tubulin protein (PDB ID: 5NM5), predicted to resemble the co-crystallized ligands GTP and Colchicine (LOC). Pharmacokinetic modeling confirmed compliance with Lipinski’s, Veber’s, and Ghose’s rules, supporting favorable drug-likeness and bioavailability. These results point to the synthesized compounds as promising candidates for the development of novel anticancer agents.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"46 3","pages":"Pages 283-302"},"PeriodicalIF":2.6,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147807227","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}

{"title":"Synthesis of New Spiropyrrolo[3,4-b]Pyridine Derivatives Employed Multicomponent Reactions","authors":"Nafiseh Tabarsa ,&nbsp;Ramin Zafar Mehrabian ,&nbsp;S. Zahra Sayyed Alangi ,&nbsp;Zinatossadat Hossaini","doi":"10.1080/10406638.2023.2273882","DOIUrl":"10.1080/10406638.2023.2273882","url":null,"abstract":"<div><div>In this research, novel derivatives of spiropyrrolo[3,4-b]pyridine derivatives were synthesized in high yields by using multicomponent reaction (MCR) of ninhydrin, ammonium acetate, ethyl 2,4-dioxo-4-arylbutanoates, primary amines, methyl propiolate, and triethyl amine (Et₃N) in aqueous media. The antioxidant activity of new synthesized spiropyrrolo[3,4-b]pyridine derivatives is due to having OH group which was evaluated by two procedures. This employed procedure for preparation of spiropyrrolo[3,4-b]pyridine derivatives conveys benefits including reaction with low time, products with high yields, and easy separation of products using an easy procedure.</div></div>","PeriodicalId":20303,"journal":{"name":"Polycyclic Aromatic Compounds","volume":"46 2","pages":"Pages 170-182"},"PeriodicalIF":2.6,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138563274","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}