Medicinal Chemistry Research最新文献

{"title":"Design, synthesis, and evaluation of benzoxathiolone derivatives as monoamine oxidase inhibitors and antibacterial agents","authors":"Bianca Coetzee,&nbsp;Stephanus J. Cloete,&nbsp;Anél Petzer,&nbsp;Jacobus P. Petzer,&nbsp;Theunis T. Cloete","doi":"10.1007/s00044-025-03450-0","DOIUrl":"10.1007/s00044-025-03450-0","url":null,"abstract":"<div><p>Benzoxathiolone derivatives have in vitro activity against monoamine oxidase A (MAO-A) and MAO-B, making them potential lead compounds for the treatment of neuropsychiatric and neurodegenerative disorders. They also have antibacterial activity against numerous bacteria. The aim of this study was to synthesise two series of benzoxathiolone derivatives with different ester (series 1) and sulfonic ester (series 2) substitutions on position C6. The in vitro half-maximal inhibitory concentration (IC₅₀) of these derivatives was determined against both MAO-A and MAO-B, after which their mode of inhibition was determined by constructing Lineweaver-Burk graphs. Additionally, the minimum inhibitory concentration (MIC) of these derivatives was also determined against <i>Staphylococcus aureus</i>, <i>Acinetobacter baumannii</i>, <i>Pseudomonas aeruginosa</i>, and <i>Escherichia coli</i>. All derivatives had activity against both MAO-A and MAO-B. With regards to MAO-A, derivatives <b>1c</b> (0.054 µM), <b>1f</b> (0.052 µM), and <b>2a</b> (0.072 µM) were the most active. The positive control, harmine (0.003 µM), was however more active. With regards to MAO-B, derivatives <b>2a</b> (0.001 µM), <b>2b</b> (0.003 µM), <b>2c</b> (0.010 µM) and <b>2d</b> (0.012 µM), were more active than both positive controls, i.e., safinamide (0.088 µM) and isatin (2.80 µM). Comparing the activity of the derivatives against MAO-A <i>versus</i> MAO-B, the sulfonic ester derivatives were more active against MAO-A while the ester derivatives were more active against MAO-B. Halide substituents on the phenyl ring notably increased MAO-A activity. For MAO-B, enhanced activity was specifically observed with <i>para</i>-position substitution on the ester derivatives. As for the antibacterial assays, only <b>1d</b> (16 µg/ml) had activity against <i>S. aureus</i>.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 9","pages":"1903 - 1913"},"PeriodicalIF":3.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-025-03450-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145171877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, and affinity evaluations of PP2A-targeting spiroketal derivatives based on structure-activity relationship studies of marine toxin okadaic acid fragments","authors":"Li Sheng,&nbsp;Rajiv Bhalla","doi":"10.1007/s00044-025-03448-8","DOIUrl":"10.1007/s00044-025-03448-8","url":null,"abstract":"<div><p>Protein phosphatase 2A (PP2A), a member of the phosphoprotein phosphatase (PPP) family, plays a pivotal role in regulating tau dephosphorylation, thereby maintaining the functional integrity of this brain-specific protein in microtubule assembly. Progressive downregulation of PP2A has been implicated in the pathogenesis of Alzheimer’s disease (AD). The identification of high-affinity PP2A ligands presents a promising avenue for monitoring early-stage dementia progression through alternative molecular mechanisms. Utilizing the catalytic binding pocket model of PP1 as a structural surrogate for PPPs, three distinct fragments derived from various natural PP2A inhibitors were found to exhibit equivalent binding functionality. Building upon this framework in small-molecule design, a synthetic spiroketal compound was developed based on the C1–C14 acidic fragment of okadaic acid (OA), a PP2A-selective inhibitor. This compound emerges as a promising candidate for further therapeutic and diagnostic investigation.</p><div><figure><div><div><picture><img></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 9","pages":"1888 - 1902"},"PeriodicalIF":3.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-025-03448-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2-azolylindoles: synthesis and evaluation of their potential as metallo-β-lactamase inhibitors","authors":"Pavel Tiuleanu,&nbsp;Ivan V. Ivanov,&nbsp;Kirill V. Rychev,&nbsp;Natalia E. Grammatikova,&nbsp;Irina P. Andreeva,&nbsp;Vitaly G. Grigorenko,&nbsp;Alexander M. Scherbakov,&nbsp;Alexey M. Egorov,&nbsp;Andrey E. Shchekotikhin","doi":"10.1007/s00044-025-03436-y","DOIUrl":"10.1007/s00044-025-03436-y","url":null,"abstract":"<div><p>Bacterial resistance to β-lactam antibiotics has emerged as a major challenge in healthcare. This form of antibiotic resistance is driven by the ability of pathogens to produce β-lactamases, which are divided into four classes (A-D) according to the Ambler classification. The most concerning are metallo-β-lactamases (MBLs) of class B, with the New Delhi Metallo-β-lactamase (NDM) enzyme family being among the most clinically significant. These zinc-dependent enzymes can inactivate almost all β-lactam antibiotics, and, to date, no effective inhibitors for this type of β-lactamase have been developed. Certain derivatives of indole-2-carboxylic acid and azoles have been shown to inhibit New Delhi metallo-β-lactamase-1 (NDM-1) by coordinating with Zn²⁺ ions and specifically interacting with key amino acid residues in the active site of the enzyme. However, the antibacterial potential of azolylindoles as metallo-β-lactamase inhibitors remains unexplored. In searches of novel scaffolds for the development of metallo-β-lactamase inhibitors a strategy for modifying a known NDM-1 inhibitor chemotype based on indole-2-carboxylic acid is proposed. This approach leads to the synthesis of previously unreported 2-azolylindoles incorporating triazole, thiadiazole, oxadiazole, tetrazole, and tetrazolylmethyl moieties. Synthetic methodologies for the preparation of intermediates and target compounds were optimized and adapted. Obtained compounds have demonstrated the ability to inhibit NDM-1 across a broad concentration range (IC₅₀ = 40 nM–15 µM), highlighting the significant influence of the azole nuclei structure on in the enzyme inhibition. The docking-predicted binding poses of the most active compounds in active site of NDM-1 closely matched with the experimental ligand orientation and revealed interactions with key amino acid residues and Zn²⁺ ions. For the most potent lead-compounds, the effect on the activity of meropenem and cefepime against NDM-1-producing strains of <i>E. coli</i> and <i>K. pneumoniae</i> was evaluated, as these antibiotics are highly relevant in antimicrobial therapy. Cytotoxicity of the synthesized series was evaluated using the noncancerous HaCaT keratinocyte cell line. The most active NDM-1 inhibitors, including the paternal acid <b>1</b> and the tetrazole analogue <b>19</b>, demonstrated low cytotoxicity (IC₅₀ &gt; 50 µM), supporting their potential as safe candidates. In contrast, compounds containing triazole, thiadiazole, or oxadiazole moieties showed increased cytotoxicity, which also limits the further development of compounds <b>25</b> and <b>26</b> as NDM-1 inhibitors. Thus, among all synthesized compounds, only 2-tetrazolylindole derivative was identified as a potential candidate for further development of novel MBL inhibitors.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 8","pages":"1714 - 1732"},"PeriodicalIF":3.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145168597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Withania coagulans: a comprehensive exploration of its botanical, phytochemical, and pharmacological properties","authors":"Azra Yasmin,&nbsp;Shammy Jindal,&nbsp;Vikramdeep Monga,&nbsp;Ghanshyam Das Gupta,&nbsp;Kamya Goyal","doi":"10.1007/s00044-025-03446-w","DOIUrl":"10.1007/s00044-025-03446-w","url":null,"abstract":"<div><p><i>Withania coagulans</i> Dunal, also known as “Indian cheese maker”, is a medicinal plant that is widely used in traditional South Asian medicine. This review illustrates a critical and comprehensive synthesis of the botanical description, phytochemistry, and pharmacological opportunities of <i>W. coagulans</i>. The intent was to assess <i>W. coagulans</i> potential for therapeutic use, focusing on safety and current knowledge gaps. Phytochemistry reports a diverse profile of withanolides, flavonoids, alkaloids, tannins, and saponins that account for the reported varied bioactivity including antidiabetic, anti-inflammatory, antimicrobial, hepatoprotective, hypolipidemic, neuroprotective, and antioxidant activities. Mechanistic studies reported various activities modulation through reported pathways such as NF-κB, MAPKs and AMPK pathways, with activity largely determined using in vitro and animal studies. While clinical studies are limited, translational potential is inhibited by identified issues such as, but not limited to, poor bioavailability and limited toxicity characterization. However, advancements in several formulations’ strategies including nanoformulations can help to bolster the pharmacokinetics parameters. This review also responded to analytical methodology for compound identification, also highlighting challenges associated with regulation and pharmaceutical development. Overall, <i>W. coagulans</i> may potentially serve as a phytopharmaceutical; nonetheless, as a priority, research studies that adhere to standardized clinical trials and systematic review will be beneficial for clinical use with evidence-based therapeutic systems.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 8","pages":"1663 - 1687"},"PeriodicalIF":3.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145169095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nutraceuticals interventions in the management of sickle cell anemia: bridging nutritional support and therapeutic strategies","authors":"Purabi Saha,&nbsp;Ritesh Jha,&nbsp;Azra Yasmin,&nbsp;Aarti Passi,&nbsp;Shammy Jindal,&nbsp;Kamya Goyal","doi":"10.1007/s00044-025-03445-x","DOIUrl":"10.1007/s00044-025-03445-x","url":null,"abstract":"<div><p>The primary cause of Sickle cell disease (SCD) is a mutation in the <i>HBB</i> gene, which plays an important role in haemoglobin production. This genetic mutation brings about the synthesis of an unusual variant of haemoglobin, haemoglobin S (HbS), which possesses a unique molecular configuration in contrast to the standard adult haemoglobin (HbA). SCD arises from an atypical HbS (α2βS2) where in the amino acid glutamic acid residue at position 6 in the β-globin chain of haemoglobin is substituted with valine. The genetic determinants of SCD include possessing two copies of the rs334 mutation (referred to as HbSS or SCA) or having one copy of the rs334 mutation in conjunction with other mutations that produce alternative forms such as mutation in the β-globin gene (e.g., HbC, cause to HbSC) or reduced β-globin production, as seen in β-thalassemia. The treatment for the management of sickle cell anemia includes hydroxyurea, folic acid, amino acid supplements, penicillin prophylaxis, antimalarial prophylaxis, and blood transfusions are the principal therapies in the clinical management of sickle cell anaemia. Investigations into the antisickling attributes of medicinal plants have yielded promising results. In vitro studies have shown that phytomedicine-based alternative therapy can reverse sickling and alleviate crises. This review focuses on identifying the diverse advantages of phytomedicines and nutraceuticals utilised in the management and treatment of sickle cell anaemia.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 8","pages":"1631 - 1662"},"PeriodicalIF":3.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145167812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and inhibitory activity against enzymes responsible for Type 2 diabetes mellitus of lactose-conjugated thiosemicarbazones from substituted acetophenones","authors":"Hoang Thi Kim Van,&nbsp;Nguyen Dinh Thanh,&nbsp;Duong Thu Nguyet","doi":"10.1007/s00044-025-03442-0","DOIUrl":"10.1007/s00044-025-03442-0","url":null,"abstract":"<div><p>An acetophenone thiosemicarbazone series <b>6a-m</b> containing lactose moiety were synthesized and explored for their inhibition against the enzymes responsible in Type 2 diabetes mellitus (T2DM), including α-amylase, α-glucosidase, DPP-4, and PTP1B. Two thiosemicarbazones exhibited the highest inhibitory activity against these enzymes, <b>6i</b> against α-glucosidase (IC₅₀ = 7.15 ± 0.12 μM) and <b>6m</b> against α-amylase, DPP-4, and PTP1B (with IC₅₀ = 7.82 ± 0.14 µM, 1.32 ± 0.02 µM, and 3.74 ± 0.14 μM when compared to the corresponding standard drugs). These compounds also exhibited the high anti-glycation and antioxidant activity in DPPH and ABTS^•+ scavenging assays. They were noncytotoxic for WI-38 cell line with IC₅₀ &gt;85 μM. Molecular docking study applied to these two most potential inhibitors on enzymes, including 3TOP for inhibitor <b>6i</b>, 1OSE, 3W2T, and 1NNY for inhibitor <b>6m</b>. These ligands had active interactions with the residues in the catalytic pocket of these corresponding enzymes that was consistent with their obtained inhibitory efficacy against each enzyme tested. The 300 ns molecular dynamics simulations applied for the complexes, including <b>6m</b>/1OSE, <b>6i</b>/3TOP, <b>6m</b>/3W2T, and <b>6m</b>/1NNY, to validate the obtained in vitro biological activity data of these inhibitors. The obtained results indicated that these inhibitors had stable dynamic interactions in the catalytic pockets of the respective enzymes to promote their activity.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 8","pages":"1746 - 1770"},"PeriodicalIF":3.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145165061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, biological evaluation, and in silico studies of chalcone-based ketamine derivatives with preferential COX-2 inhibitory activity","authors":"Syed Muzzammil Masaud,&nbsp;Humaira Nadeem,&nbsp;Abida Shamim,&nbsp;Muhammad Kazim Zargaham,&nbsp;Usman Shareef,&nbsp;Sana Ayaz,&nbsp;Babar Murtaza","doi":"10.1007/s00044-025-03444-y","DOIUrl":"10.1007/s00044-025-03444-y","url":null,"abstract":"<div><p>This study focused on synthesizing novel chalcone-ketamine derivatives and evaluation of their anti-inflammatory properties. Eighteen compounds were synthesized <i>via</i> a one-pot condensation of ketamine with various aldehydes under basic conditions. Compounds were characterized by FTIR, NMR, mass spectrometry, and elemental analysis. Molecular docking studies revealed that several of these molecules possessed low binding affinities for COX-2 than COX-1. An in vitro enzyme inhibition analysis of molecules also suggested similar trend with compounds <b>1n</b> and <b>1q</b> exhibiting the greatest preferential inhibition of COX-2 than COX-1. Key structural modifications such as specific functional groups in compounds <b>1n</b> and <b>1q</b> were identified through SAR analysis. QSAR modeling revealed a predictive correlation between structural features and inhibitory potential of synthetized molecules. Molecular dynamics (MD) simulations of the best-docked complex were carried out to assess the stability and dynamics of compound-receptor complexes followed by Molecular Mechanics Generalized Born Surface Area (MM-GBSA) calculations. Density functional theory studies were also performed on molecules <b>1n, 1q</b> and ketamine to determine the energy of frontier molecular orbitals, HOMO-LUMO band gap and Mulliken charges on the optimized structures. Significant steric and electrostatic descriptors were found to influence COX-2 selectivity. In vivo analgesic and anti-inflammatory effects of <b>1n</b> and <b>1q</b> were further evaluated in hotplate, acetic acid-induced writhing, and carrageenan-induced paw edema models, with both compounds showing significant anti-inflammatory activities. Biochemical analysis indicated significant reductions in inflammatory mediators (IL-1β, TNF-α, COX-2) in the paws of mice treated with <b>1n</b> and <b>1q</b> than disease controls. In conclusion, novel chalcone-ketamine derivatives were synthesized with preferential inhibitory activity for COX-2 than COX-1.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 8","pages":"1779 - 1805"},"PeriodicalIF":3.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-025-03444-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145165062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Excochinlignan: A new coumarino lignan from Excoecaria cochinchinensis Lour","authors":"Huong Thi Thu Le,&nbsp;Phan-Si-Nguyen Dong,&nbsp;Le-Thuy-Thuy-Trang Hoang,&nbsp;Hoai-Vu Nguyen-Si,&nbsp;Hoang-Vinh-Truong Phan,&nbsp;Thi-Minh-Thao Vo,&nbsp;Thi-Tu-Linh Tran,&nbsp;Tin-Thanh Le,&nbsp;Van-Kieu Nguyen","doi":"10.1007/s00044-025-03447-9","DOIUrl":"10.1007/s00044-025-03447-9","url":null,"abstract":"<div><p><i>Excoecaria cochinchinensis</i> Lour. is a well-known medicinal plant in Vietnam, whose parts, particularly leaves, are applied as essential medicine in folk remedies. In this study, the chemical constituents of the plant’s aerial parts, together with their feasibility in enzyme inhibition and antioxidants, were investigated. Seven compounds, including a new coumarino lignan – excochinlignan (<b>1</b>), five known flavonol derivatives (<b>2</b>-<b>6</b>) and one monophenolic (<b>7</b>), were isolated and identified <i>via</i> chromatographic and spectroscopic approaches. In vitro biological evaluation of these compounds revealed the potential of kaempferol (<b>2</b>) and its glycosides (<b>3</b>-<b>6</b>) in all assays. Among them, kaempferol (<b>2</b>) was determined as the most active antioxidant (IC₅₀ 2.86 μM) while its 3-<i>O</i>-xylose derivatives (<b>3</b>) displayed the most significant <i>α</i>-glucosidase (IC₅₀ 65.88 μM) and tyrosinase (IC₅₀ 58.97 μM) inhibition. In silico evaluation <i>via</i> molecular docking simulation suggested the supportive effect of 3-<i>O</i>-xylose, C-4′ hydroxyl and C-4 ketone moieties in the structure of the isolated flavanols (<b>2</b>-<b>6</b>) on their enzyme inhibition and antioxidant properties.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 8","pages":"1806 - 1815"},"PeriodicalIF":3.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145165063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitrofuran (E)-N’-((5-nitrofuran-2-yl)methylene)furan-2-carbohydrazide: drug candidate for the treatment of visceral toxocariasis","authors":"Débora Carvalho Rodrigues,&nbsp;Andrezza Medeiros Faria,&nbsp;Carolina Netto de Oliveira da Cunha,&nbsp;Victória Pires Panassolo,&nbsp;Lourdes Helena Rodrigues Martins,&nbsp;Thais Cristina Mendonça Nogueira,&nbsp;Marcus Vinícius Nora de Souza,&nbsp;Márcia Cristiane Feltrin Dias de Souza,&nbsp;Lívia Silveira Munhoz,&nbsp;Luciana Farias da Costa de Avila,&nbsp;Daniela Fernandes Ramos,&nbsp;Carlos James Scaini","doi":"10.1007/s00044-025-03443-z","DOIUrl":"10.1007/s00044-025-03443-z","url":null,"abstract":"<div><p>Human toxocariasis is a globally neglected parasitic disease, commonly treated with benzimidazole anthelmintics. However, their efficacy is considered unsatisfactory, requiring the research and development of new drugs. Studies have shown that hetero-cyclic compounds with nitrogenous molecules are known for their properties of inducing oxidative stress on pathogens. This study aimed to evaluate the efficacy of the (E)-N’-benzylidenefuran-2-carbohydrazide (PFUR) and ten derivatives against Toxocara canis in preclinical tests. The compounds were tested in vitro, in duplicate, at a concentration of 1.0 mg/mL to 0.062 mg/mL in a microplate containing 100 Toxocara canis larvae in RPMI-1640 medium. The compound PFUR 2 showed activity against 100% of the larvae at the minimum larvicidal concentration (MLC) of 0.25 mg/mL and was selected for the subsequent tests. Furthermore, this compound also demonstrated non-cytotoxicity to murine macrophages and an adequate estimate of oral bioavailability, as determined by the “rule of five” in computational models. After, two in vivo tests were conducted on Swiss mice. In the groups treated with PFUR 2 (10 mg/kg/5 d, IG), 10 days and 30 days after inoculation with 500 T. canis eggs, there was a reduction of 23% (p &gt; 0.05) and 62.4% (p &lt; 0.05) in the intensity of infection, respectively, compared to the PBS control. In both experiments, the PFUR 2 compound presented results similar to those of mebendazole (40 mg/kg/5 d, IG) (p &gt; 0.05). The results of this study demonstrated the potential of this compound as a candidate for a new anthelmintic.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 8","pages":"1771 - 1778"},"PeriodicalIF":3.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145163453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One-pot green synthesis of pyrazole-clubbed 2-amino-4H-pyrano[3,2-h]quinoline-3-carbonitrile derivatives as potent antimicrobial agents: in silico ADME and SAR studies","authors":"Chandani Gori,&nbsp;Dharmesh Katariya,&nbsp;Jayesh Chopda,&nbsp;Gaurav Sanghvi,&nbsp;Yogesh Naliapara","doi":"10.1007/s00044-025-03438-w","DOIUrl":"10.1007/s00044-025-03438-w","url":null,"abstract":"<div><p>The escalating challenge of antimicrobial resistance (AMR) necessitates the development of novel therapeutic agents. In this study, we present an efficient, eco-friendly, and metal-free multicomponent synthesis of a new series of pyrazole-fused 2-amino-4<i>H</i>-pyrano[3,2<i>-h</i>]quinoline-3-carbonitrile derivatives (7a–j) via a piperidine-catalyzed, solvent-free liquid-assisted grinding (LAG) method. This green synthetic approach yields the target compounds in excellent yields without the need for purification or toxic reagents. The synthesized compounds were evaluated in vitro for antimicrobial activity against gram-positive (<i>Bacillus cereus</i>, <i>Staphylococcus aureus</i>), gram-negative (<i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i>) bacteria, and pathogenic fungi (<i>Candida albicans</i>, <i>Candida tropicalis</i>). Notably, derivatives 7b, d, e, and j exhibited significant activity, with minimum inhibitory concentration (MIC) values comparable to or exceeding those of standard drugs. Structure–activity relationship (SAR) analysis and in silico ADME profiling of the active compounds (7b, d, e and j) revealed favorable pharmacokinetic and safety profiles, highlighting their potential as promising antimicrobial candidates. This work underscores the value of green synthetic methodologies in drug discovery and provides a foundation for the further development of pyrano[3,2-h] quinoline-based antimicrobial agents.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 8","pages":"1733 - 1745"},"PeriodicalIF":3.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145163228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}