European Journal of Medicinal Chemistry Reports最新文献

{"title":"New heterocyclic A1/A3 adenosine receptor ligands through molecular simplification strategies","authors":"Letizia Crocetti ,&nbsp;Abigail Pearce ,&nbsp;Venkat S. Vege ,&nbsp;Qi Xu ,&nbsp;Jing Xu ,&nbsp;Hannes Buthmann ,&nbsp;Maria Paola Giovannoni ,&nbsp;Gabriella Guerrini ,&nbsp;Francesca Catarzi ,&nbsp;Silvia Selleri ,&nbsp;Xianglin Huang ,&nbsp;Aneesh Chandran ,&nbsp;Graham Ladds ,&nbsp;Agostino Cilibrizzi","doi":"10.1016/j.ejmcr.2025.100253","DOIUrl":"10.1016/j.ejmcr.2025.100253","url":null,"abstract":"<div><div>In this paper we report the synthesis of new A₁/A₃ adenosine receptor antagonists designed as simplification products of the A₁ antagonists with pyrazolo[1′,5′:1,6]pyrimido [4,5-d]pyridazin-4(3H)-one scaffold previously developed by us. Notably, selective A₁R antagonists are promising therapeutic agents in Alzheimer's disease and for the treatment of cognitive deficits, while A₃R antagonists are potentially useful in the treatment of ischemia and certain types of cancer. Initial screening with NanoBRET competition binding assay revealed a number of products with pKi ≥5 for A₁R and A₃R. For some representative compounds the antagonist profiles, as well as their selectivity versus A_2AR and A_2BR, have been also validated by antagonizing NECA in cAMP accumulation. The most interesting compounds resulted the A₁/A₃ mixed antagonist <strong>3b</strong> (pKi = 6.41 and 6.29 for A₁R and A₃R respectively, pKb = 5.00 and 5.27 for the A_2aR and A_2bR) and the selective A₃R antagonist <strong>5c</strong> (pKi = 6.40, pKb values of 4.44, 6.17, 4.16, and 4.78 for the A₁R, A₃R, A_2aR and A_2bR, respectively). Furthermore, <em>in silico</em> simulations were carried out to study the molecular mechanism of the high affinity of <strong>3b</strong> for A₁/A₃Rs as well as the selectivity of <strong>5c</strong> for A₃R over A₁R. Overall, this work highlights new series of bicyclic small-molecules as valid candidates for further structural optimization towards the development of therapeutically relevant A₁/A₃ adenosine receptor antagonists.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"13 ","pages":"Article 100253"},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural products combating EGFR-TKIs resistance in cancer","authors":"Li Xia ,&nbsp;Gaohui Zhu ,&nbsp;Qiyao Peng ,&nbsp;Xiuyang Li ,&nbsp;Xinrong Zou ,&nbsp;Wanping Zhang ,&nbsp;Lulu Zhao ,&nbsp;Xiong Li ,&nbsp;Ping Wu ,&nbsp;Aimin Luo ,&nbsp;Teng Yang ,&nbsp;Meizi Chen ,&nbsp;Teng Liu ,&nbsp;Yongbo Peng","doi":"10.1016/j.ejmcr.2025.100251","DOIUrl":"10.1016/j.ejmcr.2025.100251","url":null,"abstract":"<div><div>The role of natural products in cancer treatment has received substantial attention. Significantly, natural products can interact with multiple targets, which is meaningful in overcoming drug resistance synergistically. Resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is a significant cause of treatment failure in non-small cell lung cancer (NSCLC). In this review, we summarize the main resistance mechanisms to EGFR-TKIs and present that 67 reported natural products (from 2005 to 2024) demonstrate the potential to combat EGFR-TKIs resistance in cancer via at least 30 pathways, mainly including ROS, PD-L1, EGFR, MAPK, mTOR, HSP90, JNK, PTEN, and FOXO. Based on the rule of five evaluation of druggability, we can obtain 37 natural products suitable for further development. This review aims to systematically summarize recent advances of natural products in overcoming EGFR-TKIs resistance, and provide some inspirations for novel drug discovery in cancer including NSCLC.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"13 ","pages":"Article 100251"},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis and evaluation of quinazoline-chalcone hybrids as inducers of cell-cycle arrest and apoptosis in breast cancer via DNA damage and CDK2/ATR inhibition","authors":"Giulia Rodrigues Stringhetta ,&nbsp;Eduardo Bustos Mass ,&nbsp;Izabela Natalia Faria Gomes ,&nbsp;Maria Clara Fonseca Peixoto ,&nbsp;Amanda Helena Tejada ,&nbsp;Luciane Susucchi ,&nbsp;Aryel José Alves Bezerra ,&nbsp;Pedro Victor Silva Resende ,&nbsp;Vinicius Vendrúsculo ,&nbsp;Rui Manuel Reis ,&nbsp;Dennis Russowsky ,&nbsp;Renato José Da Silva Oliveira","doi":"10.1016/j.ejmcr.2025.100250","DOIUrl":"10.1016/j.ejmcr.2025.100250","url":null,"abstract":"<div><div>In this study, a series of novel hybrid compounds, 2-arylquinazolinechalcones, were synthesized and their antitumoral activities were evaluated. Among them, compounds <strong>7b</strong> and <strong>7n</strong> exhibited the highest cytotoxicity and selectivity rates for the triple-negative breast cancer cell line MDA-MB-231. In 3D spheroid culture, <strong>7b</strong> and <strong>7n</strong> decreased viability and increased cell death. Both compounds induced cell death primarily through the extrinsic pathway and promoted cell cycle arrest in G0/G1, possibly through increased expression of p27 and subsequent reduction in CDK2 levels. Additionally, they may trigger oxidative stress and DNA damage, as evidenced by elevated levels of H2AX activation, and compromise DNA repair pathways mediated by ATR and CHK1. To further explore the mechanism behind the observed cell cycle arrest, we performed phospho-RTK and phospho-MAPK Reverse Phase Protein Arrays to investigate changes in the expression of activated RTKs and MAPKs after treatment with <strong>7b</strong> and <strong>7n</strong>, compared to the negative control. These findings suggest that <strong>7b</strong> and <strong>7n</strong> are promising candidates for further development as targeted therapies for triple-negative breast cancer.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"13 ","pages":"Article 100250"},"PeriodicalIF":0.0,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological evaluation of novel 5-((1H-indol-3-yl) methyl)-2-(4-chlorobenzyl)-6-phenyl-imidazo[2,1-b][13,4]thiadiazole derivatives as novel BCL-2 specific inhibitors","authors":"Shivangi Sharma ,&nbsp;Sadashivamurthy Shamanth ,&nbsp;Humaira Siddiqua ,&nbsp;Laijau Goyary ,&nbsp;Kunigal S. Sagar ,&nbsp;Susmita Kumari ,&nbsp;Divya Sathees ,&nbsp;Gudapureddy Radha ,&nbsp;Bibha Choudhary ,&nbsp;Sathees C. Raghavan ,&nbsp;Kempegowda Mantelingu","doi":"10.1016/j.ejmcr.2025.100247","DOIUrl":"10.1016/j.ejmcr.2025.100247","url":null,"abstract":"<div><div>Antiapoptotic protein BCL2 is known to be upregulated in several cancer cells and therefore, it is an excellent target for cancer therapy. Previously, we reported a novel BCL2 inhibitor, Disarib, which inhibited BCL2 by predominantly binding to its BH1 domain and exhibited platelet-sparing ability like ABT199, the only FDA-approved BCL2 inhibitor. Here, we have synthesized the novel Disarib derivatives where oxindole moiety in Disarib was replaced with indole and evaluated their biological activity. We report several derivatives of Disarib and the identification of DSR 43 and 4-OCH₃, as the most potent among them. Treatment of cancer cell lines with the Disarib derivatives, DSR 43 and 4-OCH₃ led to the activation of the apoptotic pathway without generating any ROS or disrupting the mitochondrial membrane potential within the cells, leading to cell death. Western blot analysis in tandem with Annexin V/PI staining confirmed the activation of apoptosis. <em>In silico</em> studies, using derivatives suggests a promising therapeutic window with less off-target effects. Furthermore, their efficacy across different cancer cell lines highlights their broad potential as anticancer agents. Taken together, our results suggest that Disarib derivatives may have the potential to be developed as cancer therapeutic.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"13 ","pages":"Article 100247"},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143160279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, evaluation of the biological activity against Trypanosoma cruzi and Leishmania donovani. Preliminary in silico ADMET studies of 5-nitroimidazole derivatives","authors":"Miguel A. Rodríguez ,&nbsp;Ali Mijoba ,&nbsp;Nereida J. Parra-Giménez ,&nbsp;Zuleyma Blanco ,&nbsp;Katiuska Chávez ,&nbsp;Alirica I. Suárez ,&nbsp;Esteban Fernandez-Moreira ,&nbsp;Hegira Ramírez ,&nbsp;Jaime E. Charris","doi":"10.1016/j.ejmcr.2025.100248","DOIUrl":"10.1016/j.ejmcr.2025.100248","url":null,"abstract":"<div><div>The synthesis and evaluation of the biological activity of a series of 5-nitroimidazole hybrids is described. The structures of the synthesized hybrids were confirmed by spectral analysis FT-IR, ¹H NMR, ¹³C NMR, MS, and by Elemental Analysis. The toxicity (ADME/Tox) assessment study were carried out to predict the molecular properties associated with pharmacokinetic aspects of novel compounds. The trypanocidal and leishmanicidal activities of all synthesized hybrids were evaluated, compounds <strong>7a</strong> and <strong>8b</strong> were active against the epimastigote form of <em>T. cruzi</em>. Compound <strong>10b</strong> showed marginal activity against the promastigote form of <em>L. donovani</em>. Sulfonyl derivative <strong>8b</strong> was the most promising compound with IC₅₀: 9.58 ± 2.02 μM and with a selectivity index (SI) greater than 31.31, that justifies the description as a promising hit for further study as a possible antichagasic agent.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"13 ","pages":"Article 100248"},"PeriodicalIF":0.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143264575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P-glycoprotein-independent cytotoxic effects of 5-aminopyrazole in L1210 leukemia cells","authors":"Lucia Sofrankova ,&nbsp;Jana Spaldova ,&nbsp;Pavol Stefik ,&nbsp;Branislav Pavilek ,&nbsp;Dusan Bortnak ,&nbsp;Lucia Pavlikova ,&nbsp;Ivana Zidekova ,&nbsp;Daniel Vegh ,&nbsp;Viktor Milata ,&nbsp;Albert Breier ,&nbsp;Zdena Sulova","doi":"10.1016/j.ejmcr.2025.100246","DOIUrl":"10.1016/j.ejmcr.2025.100246","url":null,"abstract":"<div><div>We previously investigated the cytotoxic effects of 5-aminopyrazoles (5-APs) on leukemia cells both negative and positive for P-glycoprotein (P-gp) expression, a common contributor to multidrug resistance. Five derivatives (A1-A5), each containing perfluorinated methylbenzene at the N3 nitrogen of the pyrazole ring, were tested on murine lymphoblastic cell line variants: parental S cells (P-gp positive), R cells (vincristine-resistant and P-gp positive), and T cells (human P-gp transfected). Among these, A1 and A4 exhibited the strongest effects, especially in R cells, with lesser but similar effects observed in S and T cells. Cell death assays revealed both apoptosis and necrosis, with apoptosis confirmed by DNA fragmentation and activation of caspases 3/7, 8, and, to a lesser extent, 9, suggesting a predominance of extrinsic apoptosis. The compounds also induced autophagy, identified by LysoTracker Green and monodansylcadaverine staining. All derivatives, except A5, suppressed P-gp activity, though they did not alter P-gp expression at the mRNA or protein level. Cell cycle analysis showed changes in the G0/G1 and S phases. The heightened sensitivity of R cells to 5-AP, despite P-gp expression, likely results from an altered phenotype due to vincristine-induced stress rather than from P-gp inhibition alone. This conclusion is supported by the fact that T cells expressing P-gp are as sensitive to 5-APs as S cells.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"13 ","pages":"Article 100246"},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143160278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, In vitro antimicrobial activity, and In silico bioinformatical approach of xanthone-fatty acid esters against Staphylococcus aureus, Escherichia coli, and Candida albicans","authors":"Yehezkiel Steven Kurniawan ,&nbsp;Ervan Yudha ,&nbsp;Jumina ,&nbsp;Harno Dwi Pranowo ,&nbsp;Eti Nurwening Sholikhah","doi":"10.1016/j.ejmcr.2025.100245","DOIUrl":"10.1016/j.ejmcr.2025.100245","url":null,"abstract":"<div><div>Microbial infection is gaining attention nowadays due to a high number of active cases and mortality rate. Because of that, research in finding new antimicrobial agents is urgently needed. In this work, we combined the chemical structure of 3-hydroxyxanthone and some fatty acids through ester linkage to form xanthyl laurate, xanthyl myristate, xanthyl palmitate, xanthyl stearate, and xanthyl oleate in 78.68–89.77 % yield. The <em>in vitro</em> antimicrobial assay revealed that xanthyl laurate exhibited the strongest antimicrobial activity with zone of inhibition of 11.0 ± 1.65, 9.43 ± 1.74, and 9.30 ± 1.37 mm against <em>Staphylococcus aureus</em>, <em>Escherichia coli</em>, and <em>Candida albicans</em>, respectively, which also higher than 3-hydoxyxanthone and lauric acid. Xanthyl laurate also yielded minimum inhibition concentration values of 31.25–62.50 μg/mL, which was 2 times lower than of 3-hydroxyxanthone. The structure-based bioinformatical approach indicated that ftsZ <em>S. aureus</em>, MAPK <em>E. coli</em>, and PDE <em>C. albicans</em> are the potential target for xanthyl laurate. Furthermore, both molecular docking and molecular dynamic simulations indicated good stability of xanthyl laurate in the active site of each protein receptor through hydrogen bond and other non-covalent interactions. The <em>in vitro</em> cytotoxicity assay against the NIH3T3 cell line showed that xanthyl laurate was non-toxic at 500 μg/mL with a cell viability percentage of 86.14 ± 1.38 %. This study reports that xanthyl laurate is the most potential antimicrobial agent based on the xanthone-fatty acid ester's structure against <em>S. aureus</em>, <em>E. coli</em>, and <em>C. albicans</em> in both <em>in vitro</em> and <em>in silico</em> assays.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"13 ","pages":"Article 100245"},"PeriodicalIF":0.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143160277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation and pharmacological characterization of the enantiomers of the anticancer agent R/S-N-3-cyanophenyl-N'-(6-tert-butoxycarbonylamino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)urea: Identification of the R-enantiomer as the active eutomer","authors":"Michael Schnekenburger ,&nbsp;Eric Goffin ,&nbsp;Matthieu Schoumacher ,&nbsp;Nikolay Tumanov ,&nbsp;Ange Mouithys-Mickalad ,&nbsp;Pascal de Tullio ,&nbsp;Johan Wouters ,&nbsp;Philippe Lebrun ,&nbsp;Marc Diederich ,&nbsp;Bernard Pirotte","doi":"10.1016/j.ejmcr.2024.100244","DOIUrl":"10.1016/j.ejmcr.2024.100244","url":null,"abstract":"<div><div>R/S-N-3-cyanophenyl-N'-(6-tert-butoxycarbonylamino-3,4-dihydro-2,2-dimethyl-2<em>H</em>-1-benzopyran-4-yl)urea (BPDZ 711, <strong>4</strong>) initially designed as a K_ATP channel opener, was found to exhibit diverse biological activities. The compound inhibited insulin release from rat pancreatic islets, indicating a potential effect on glucose metabolism. Oxygraphy measurements on chronic myeloid leukemia (CML) K-562 cells revealed an impact on cellular respiration. Additionally, the compound demonstrated inhibitory activity on histone deacetylase class III enzymes (sirtuins), linking metabolic and epigenetic regulation. This was corroborated by its effect on protein acetylation and modulation of the extracellular pH of treated CML cells. Alterations in CML cells' nuclear morphology and the release of high-mobility group box 1 (HMGB1) protein confirmed mechanisms related to cellular stress and immunogenic cell death. BPDZ 711 preserved the viability of peripheral blood mononuclear cells, thus demonstrating excellent differential toxicity.</div><div>Since BPDZ 711 is a racemate, the present study focused on the preparation of the two enantiomers and examined the possibility that each isomer could display a distinct pharmacological profile. Our data revealed that the R-enantiomer (<strong>5</strong>) of BPDZ 711 was consistently the most biologically active compound (eutomer), making it the reference compound for future drug discovery and development.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"13 ","pages":"Article 100244"},"PeriodicalIF":0.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143160324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photochemical internalization of mRNA using a photosensitizer and nucleic acid carriers","authors":"Hayaki Maemoto ,&nbsp;Ryohei Suzaki ,&nbsp;Kazunori Watanabe ,&nbsp;Keiji Itaka ,&nbsp;Takashi Ohtsuki","doi":"10.1016/j.ejmcr.2024.100242","DOIUrl":"10.1016/j.ejmcr.2024.100242","url":null,"abstract":"<div><div>mRNA has great potential for therapeutic applications because it can encode a variety of proteins and antigens, in addition to advantages over DNA in terms of gene expression without genomic integration, nuclear localization, or transcription. However, therapeutic applications of mRNA require safe and effective delivery into target cells. Therefore, we aimed to investigate photochemical internalization (PCI) as a promising strategy for delivering mRNA to target cells. In this strategy, mRNA is taken up into cells by endocytosis, accumulates in endosomes, and is released in a light-dependent manner from the endosomes using an endosome-accumulating photosensitizer, aluminum phthalocyanine disulfonate (AlPcS_2a), in combination with nucleic acid carrier molecules. We compared the efficacy of various nucleic acid carriers, including branched polyethyleneimine (bPEI) and poly{N'-[N-(2-aminoethyl)-2-aminoethyl] aspartamide} (PAsp(DET)) under the same conditions for PCI-based mRNA delivery. Our results indicated that bPEI and PAsp(DET) at low N/P ratios exhibited efficient light-enhancement of mRNA expression by PCI with AlPcS_2a. Notably, bPEI exhibited the highest light-dependent mRNA delivery among the carriers evaluated (including cationic polymers, cationic peptides, and lipids), whereas PAsp(DET) showed promise for clinical use because of its lower toxicity compared with bPEI. This PCI strategy allows effective cytosolic mRNA delivery at low N/P ratios, thereby reducing cationic carrier molecule-induced cytotoxicity. This method allows spatiotemporal control of protein expression and holds potential for novel light-dependent mRNA therapies. Overall, this study provided valuable insights into optimizing mRNA delivery systems for therapeutic applications.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"13 ","pages":"Article 100242"},"PeriodicalIF":0.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143160280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and in vitro/in silico evaluation of the antimalarial activity of potential amino-quinoline derivatives","authors":"Moussa Touré ,&nbsp;Abdoulaye Gassama ,&nbsp;Oumar Sambou ,&nbsp;Christian Cavé ,&nbsp;Sandrine Cojean","doi":"10.1016/j.ejmcr.2024.100241","DOIUrl":"10.1016/j.ejmcr.2024.100241","url":null,"abstract":"<div><div>In this study, a series of <em>N</em>-arylamino-7-chloroquinolines were synthesized via an alkylation reaction involving aniline derivatives <strong>(2)</strong> and 4,7-dichloroquinoline <strong>(1)</strong>. Additionally, the synthesis of a library of <em>N</em>-aryl-<em>N</em>-benzylamino-7-chloroquinoline analogues, modified on the aniline nitrogen, has also reported. A structure-activity relationship (SAR) study was conducted to evaluate the biological efficacy and safety of these derivatives against chloroquine-sensitive (<em>Pf</em>3D7) and chloroquine-resistant (<em>Pf</em>W2) <em>Plasmodium falciparum</em> strains. Compounds <strong>5i</strong> and <strong>5c</strong> showed promising efficacy against the <em>Pf</em>3D7 strain with IC₅₀ values of 0.25 μM and 0.54 μM, respectively, while compound <strong>5l</strong> demonstrated significant activity against the <em>Pf</em>W2 strain with an IC₅₀ of 5.82 μM. The cytotoxicity of these compounds was also evaluated on HUVEC cell lines. Additionally, their pharmacological and pharmacokinetic (ADME) properties were studied to predict their fate and identify promising candidates for further clinical studies.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"13 ","pages":"Article 100241"},"PeriodicalIF":0.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143160325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}