Acta Pharmaceutica最新文献_第5页

Furanocoumarin compounds isolated from Dorstenia foetida potentiate irinotecan anticancer activity against colorectal cancer cells. 从 Dorstenia foetida 中分离出的呋喃香豆素化合物可增强伊立替康对结直肠癌细胞的抗癌活性。

IF 2.8 4区医学

Acta Pharmaceutica Pub Date : 2024-03-30 Print Date: 2024-03-01 DOI: 10.2478/acph-2024-0004

Supusson Pengnam, Watcharapa Jitkaroon, Roongtiwa Srisuphan, Pawaris Wongprayoon, Kanok-On Rayanil, Purin Charoensuksai

{"title":"Furanocoumarin compounds isolated from Dorstenia foetida potentiate irinotecan anticancer activity against colorectal cancer cells.","authors":"Supusson Pengnam, Watcharapa Jitkaroon, Roongtiwa Srisuphan, Pawaris Wongprayoon, Kanok-On Rayanil, Purin Charoensuksai","doi":"10.2478/acph-2024-0004","DOIUrl":"10.2478/acph-2024-0004","url":null,"abstract":"Although the anticancer activity of Dorstenia foetida was already observed, the chemical entity responsible for this activity remained unidentified. In this study, the cytotoxic activity of two furanocoumarin compounds, i.e., 5-methoxy--3-(3-methyl-2,3-dihydroxybutyl)-psoralen (1) and 5-methoxy-3-(3-methyl-2,3-dihydroxybutyl)-psoralen diacetate (2) isolated from ethyl acetate fraction of D. foetida (whole plant) was investigated in several cancer cell lines including HN22, MDA-MB-231, HCT116, and HT29. The results revealed that compound 2 exhibited cytotoxic activity, particularly against colorectal cancer cell lines HCT116 and HT29. The interplay between compound 2 and irinotecan (Iri) showed synergism against HCT116, which was analyzed by CompuSyn software. The simulation revealed that, at the molar ratio of Iri:2 of 1:40, the concentration predicted to achieve a 90 % inhibitory effect when used in the combination would be ~28- and ~4-fold lower than the concentration of compound 2 and Iri, resp., when used individually. Finally, the percentage of apoptotic cells in the HCT116 line treated with the combination was markedly higher than in the cells treated with the individual agent (60 % apoptotic cells for the combination compared to 17 and 45 % for Iri and compound 2 monotherapy, resp). In conclusion, our results identified compound 2 as a plant-derived compound exhibiting anticancer properties that can act synergistically with Iri and warranted further research to assess the potential of this synergism for colorectal cancer treatment.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 1","pages":"67-79"},"PeriodicalIF":2.8,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329473","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}

引用次数: 0

Characterization of mineral composition of leaves and flowers of wild-growing Sambucus nigra. 野生西洋接骨木叶和花矿物质成分的特征。

IF 2.8 4区医学

Acta Pharmaceutica Pub Date : 2024-03-30 Print Date: 2024-03-01 DOI: 10.2478/acph-2024-0007

Bujar Qazimi, Trajče Stafilov, Katerina Bačeva Andonovska, Krste Tašev, Nikola Geskovski, Shpend Dragusha, Hyrije Koraqi, Valon Ejupi

引用次数: 0

A comprehensive overview of selective and novel fibroblast growth factor receptor inhibitors as a potential anticancer modality. 选择性和新型成纤维细胞生长因子受体抑制剂作为一种潜在抗癌方式的全面概述。

IF 2.8 4区医学

Acta Pharmaceutica Pub Date : 2024-03-30 Print Date: 2024-03-01 DOI: 10.2478/acph-2024-0005

Nem Kumar Jain, Mukul Tailang, Neelaveni Thangavel, Hafiz A Makeen, Mohammed Albratty, Asim Najmi, Hassan Ahmad Alhazmi, Khalid Zoghebi, Muthumanickam Alagusundaram, Hemant Kumar Jain, Balakumar Chandrasekaran

{"title":"A comprehensive overview of selective and novel fibroblast growth factor receptor inhibitors as a potential anticancer modality.","authors":"Nem Kumar Jain, Mukul Tailang, Neelaveni Thangavel, Hafiz A Makeen, Mohammed Albratty, Asim Najmi, Hassan Ahmad Alhazmi, Khalid Zoghebi, Muthumanickam Alagusundaram, Hemant Kumar Jain, Balakumar Chandrasekaran","doi":"10.2478/acph-2024-0005","DOIUrl":"10.2478/acph-2024-0005","url":null,"abstract":"The arrival of comprehensive genome sequencing has accelerated the understanding of genetically aberrant advanced cancers and target identification for possible cancer treatment. Fibroblast growth factor receptor (FGFR) gene alterations are frequent findings in various rare and advanced cancers refractive to mainstay chemo-therapy or surgical interventions. Several FGFR inhibitors have been developed for addressing these genetically altered FGFR-harboring malignancies, and some have performed well in clinical trials. In contrast, others are still being investigated in different phases of clinical trials. FDA has approved four anticancer agents such as erdafitinib, pemigatinib, infigratinib, and futibatinib, for clinical use in oncogenic FGFR-driven malignancies. These include cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid malignancies. Pemigatinib is the only FGFR inhibitor globally approved (USA, EU, and Japan) and available as a targeted therapy for two types of cancer, including FGFR2 fusion or other rearrangements harboring cholangiocarcinoma and relapsed/refractory myeloid/lymphoid neoplasms with FGFR1 rearrangements. Myeloid/lymphoid neoplasm is the latest area of application added to the therapeutic armamentarium of FGFR inhibitors. Furthermore, futibatinib is the first-in-class covalent or irreversible pan-FGFR inhibitor that has received FDA approval for locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene aberrations. This review highlights the current clinical progress concerning the safety and efficacy of all the approved FGFR-TKIs (tyrosine kinase inhibitors) and their ongoing investigations in clinical trials for other oncogenic FGFR-driven malignancies.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 1","pages":"1-36"},"PeriodicalIF":2.8,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329468","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}

引用次数: 0

Azithromycin-loaded liposomal hydrogel: a step forward for enhanced treatment of MRSA-related skin infections. 阿奇霉素脂质体水凝胶：在加强治疗 MRSA 相关皮肤感染方面向前迈进了一步。

IF 2.8 4区医学

Acta Pharmaceutica Pub Date : 2023-12-26 Print Date: 2023-12-01 DOI: 10.2478/acph-2023-0042

Zora Rukavina, May Wenche Jøraholmen, Dunja Božić, Ivana Frankol, Petra Golja Gašparović, Nataša Škalko-Basnet, Maja Šegvić Klarić, Željka Vanić

{"title":"Azithromycin-loaded liposomal hydrogel: a step forward for enhanced treatment of MRSA-related skin infections.","authors":"Zora Rukavina, May Wenche Jøraholmen, Dunja Božić, Ivana Frankol, Petra Golja Gašparović, Nataša Škalko-Basnet, Maja Šegvić Klarić, Željka Vanić","doi":"10.2478/acph-2023-0042","DOIUrl":"10.2478/acph-2023-0042","url":null,"abstract":"Azithromycin (AZT) encapsulated into various types of liposomes (AZT-liposomes) displayed pronounced in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA) (1). The present study represents a follow-up to this previous work, attempting to further explore the anti-MRSA potential of AZT-liposomes when incorporated into chitosan hydrogel (CHG). Incorporation of AZT-liposomes into CHG (liposomal CHGs) was intended to ensure proper viscosity and texture properties of the formulation, modification of antibiotic release, and enhanced antibacterial activity, aiming to upgrade the therapeutical potential of AZT-liposomes in localized treatment of MRSA-related skin infections. Four different liposomal CHGs were evaluated and compared on the grounds of antibacterial activity against MRSA, AZT release profiles, cytotoxicity, as well as texture, and rheological properties. To our knowledge, this study is the first to investigate the potential of liposomal CHGs for the topical localized treatment of MRSA-related skin infections. CHG ensured proper viscoelastic and texture properties to achieve prolonged retention and prolonged release of AZT at the application site, which resulted in a boosted anti-MRSA effect of the entrapped AZT-liposomes. With respect to anti-MRSA activity and biocompatibility, formulation CATL-CHG (cationic liposomes in CHG) is considered to be the most promising formulation for the treatment of MRSA-related skin infections.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"73 4","pages":"559-579"},"PeriodicalIF":2.8,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039335","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}

引用次数: 0

Functionalization of selenium nanoparticles with olive polyphenols - impact on toxicity and antioxidative activity. 硒纳米颗粒与橄榄多酚的功能化--对毒性和抗氧化活性的影响。

IF 2.8 4区医学

Acta Pharmaceutica Pub Date : 2023-12-26 Print Date: 2023-12-01 DOI: 10.2478/acph-2023-0036

Emerik Galić, Kristina Radić, Nikolina Golub, Jakov Mlinar, Dubravka Vitali Čepo, Tomislav Vinković

{"title":"Functionalization of selenium nanoparticles with olive polyphenols - impact on toxicity and antioxidative activity.","authors":"Emerik Galić, Kristina Radić, Nikolina Golub, Jakov Mlinar, Dubravka Vitali Čepo, Tomislav Vinković","doi":"10.2478/acph-2023-0036","DOIUrl":"10.2478/acph-2023-0036","url":null,"abstract":"Selenium nanoparticles (SeNPs) represent novel selenium (Se) formulation characterized by improved biocompatibility and a wider therapeutic range in comparison to inorganic Se. The aim of this work was to investigate the possibilities of functionalization of SeNPs with olive pomace extract (OPE), rich in health-promoting polyphenols, and to obtain innovative forms of nutraceuticals. Cytotoxic and antioxidative activities of four types of SeNPs (polyvinylpyrrolidone stabilized (PVP SeNPs), polysorbate stabilized (PS SeNPs), polyvinylpyrrolidone stabilized and functionalized using OPE (f PVP SeNPs) and polysorbate stabilized and functionalized using OPE (f PS SeNPs) were investigated. SeNPs showed lower toxicity on human hepatocellular carcinoma (HepG2) and human colorectal adenocarcinoma (Caco2) cells compared to selenite. Functionalization with polyphenols significantly improved their direct antiradical (f PVP SeNPs: 24.4 ± 1.84 and f PS SeNPs: 30.9 ± 2.47 mg TE/mmol Se) and reducing properties (f PVP SeNPs: 50 ± 3.16 and f PS SeNPs: 53.6 ± 3.22 mg GAE/mmol) compared to non-functionalized SeNPs. The significant impact of tested SeNPs on intracellular antioxidative mechanisms has been observed and it was dependent on both cell type and physico-chemical properties of SeNPs, indicating the complexity of involved mechanisms.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"73 4","pages":"617-631"},"PeriodicalIF":2.8,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039339","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}

引用次数: 0

Oleuropein in olive leaf, branch, and stem extracts: stability and biological activity in human cervical carcinoma and melanoma cells. 橄榄叶、枝和茎提取物中的油菜素：在人类宫颈癌和黑色素瘤细胞中的稳定性和生物活性。

IF 2.8 4区医学

Acta Pharmaceutica Pub Date : 2023-12-26 Print Date: 2023-12-01 DOI: 10.2478/acph-2023-0046

Đani Benčić, Monika Barbarić, Ana Mornar, Daniela Amidžić Klarić, Anamaria Brozovic, Sanja Dabelić, Mihaela Fadljević, Ana Karković Marković

{"title":"Oleuropein in olive leaf, branch, and stem extracts: stability and biological activity in human cervical carcinoma and melanoma cells.","authors":"Đani Benčić, Monika Barbarić, Ana Mornar, Daniela Amidžić Klarić, Anamaria Brozovic, Sanja Dabelić, Mihaela Fadljević, Ana Karković Marković","doi":"10.2478/acph-2023-0046","DOIUrl":"10.2478/acph-2023-0046","url":null,"abstract":"Olive leaves as a main byproduct of olive oil and fruit industry are a valuable source of phytochemicals such as polyphenols, with multiple biomedical effects. Apart from leaves, olive branches and stems make up a significant amount of olive waste. It is well known that the drying process and long-term storage affect the stability and concentration of polyphenols present in raw materials. For that matter, two different means of storing olive waste, at room temperature and +4 °C, were compared by determining the content of the polyphenol oleuropein (OLE) in olive leaf, branch, and stem extracts (LE, BE, and SE) by HPLC-DAD method. Total phenols (TPC), o-diphenols (o-DPC), and total flavonoids (TFC) content in extracts were assessed by UV-Vis measurements. LE prepared from leaves stored at +4 °C had the highest OLE content, 30.7 mg g-1 of dry extract (DE). SE from stems stored at +4 °C was the richest in TPC and TFC (193 mg GAE/g DE and 82.9 mg CE/g DE, respectively), due to the higher purity of the extract. The biological activity of extracts was determined on cervical cancer (HeLa), melanoma (A375), metastatic melanoma (A375M) tumor cell lines, and on spontaneously immortalized cell line of keratinocytes (HaCaT), using the MTT assay. The data show that all extracts had a similar dose-dependent effect on cell viability in HeLa cells, while the effect of LE on melanoma A375 and A375M, and HaCaT cells was cell-line dependent.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"73 4","pages":"601-616"},"PeriodicalIF":2.8,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039341","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}

引用次数: 0

Size exclusion chromatography as green support for forced degradation study of adalimumab. 尺寸排阻色谱法作为阿达木单抗强制降解研究的绿色支持。

IF 2.8 4区医学

Acta Pharmaceutica Pub Date : 2023-12-26 Print Date: 2023-12-01 DOI: 10.2478/acph-2023-0044

Jelena Kovačić, Daniela Amidžić Klarić, Nikša Turk, Ana Mornar

{"title":"Size exclusion chromatography as green support for forced degradation study of adalimumab.","authors":"Jelena Kovačić, Daniela Amidžić Klarić, Nikša Turk, Ana Mornar","doi":"10.2478/acph-2023-0044","DOIUrl":"10.2478/acph-2023-0044","url":null,"abstract":"Size exclusion chromatography (SEC) has become a powerful tool for analysing size variants of biologic drugs in their native form. Modern SEC can be defined by the use of chromatographic columns packed with sub-3 µm particles, allowing an increase in method throughput compared to that of conventional SEC. We performed the forced degradation study of adalimumab, the first genetically engineered fully humanised immunoglobulin G1 monoclonal antibody, and evaluated tha possibilities of an advanced SEC column packed with sub-3 µm particles for elucidation of the degradation pathway. Our results revealed the main adalimumab degradation products to be antibody fragments. Acidic and basic conditions had the most intensive effect on the degradation of the adalimumab while the drug exhibits relative stability under thermal and photolytic stress conditions. The AGREE and AGREEprep calculators were used for the evaluation of the environmental performance of the forced degradation procedure. The results of the green score evaluation are presented as round pictograms with a circle in the centre that shows the overall score of 0.81 and 0.61, respectively. Both pictograms are highlighted in green, indicating the eco-friendly conditions.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"73 4","pages":"709-721"},"PeriodicalIF":2.8,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039345","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}

引用次数: 0

The impact of cryoprotectant exposure time on post-thaw viability of autologous and allogeneic hematopoietic stem cells and leukocyte subpopulations. 低温保护剂暴露时间对自体和异体造血干细胞及白细胞亚群解冻后存活率的影响。

IF 2.8 4区医学

Acta Pharmaceutica Pub Date : 2023-12-26 Print Date: 2023-12-01 DOI: 10.2478/acph-2023-0037

Vladimira Rimac, Ines Bojanić, Sanja Dabelić, Branka Golubić Ćepulić

{"title":"The impact of cryoprotectant exposure time on post-thaw viability of autologous and allogeneic hematopoietic stem cells and leukocyte subpopulations.","authors":"Vladimira Rimac, Ines Bojanić, Sanja Dabelić, Branka Golubić Ćepulić","doi":"10.2478/acph-2023-0037","DOIUrl":"10.2478/acph-2023-0037","url":null,"abstract":"Although the use of cryoprotectant dimethyl sulfoxide (DMSO) is the gold standard in cryopreservation of hematopoietic stem cells, it is well known that it has a negative effect on cell viability. The aim of this prospective study was to examine how the length of post-thaw exposure to DMSO affects the cell viability and stability of peripheral blood stem cell (PBSC) samples. Additionally, the effects of donor type and pre-cryopreservation storage time on post-thaw viability during the stability study were evaluated. In 30 autologous and 30 allogeneic PBSC samples viable CD34+, CD14+, CD19+, CD16+/56+, and CD3+ cells were determined immediately after thawing, and one-and three-hours post-thaw. Analysis of the absolute count of viable cells in thawed samples showed a significant difference between all measurement points for CD34+ (p < 0.001), CD14+ (p < 0.001), and CD19+ cells (p < 0.001). No significant differences were observed for post-thaw stability of allogeneic samples analysed between products stored before cryopreservation ≥ 24 hours (N = 20), and those stored < 24 hours (N = 10), except for viable CD3+/CD4+ cells after three hours post-thaw (p = 0.028). In conclusion, DMSO had different effects on leukocyte subpopulations in cryopre-served PBSC samples. The type of donors and the length of storage before cryopreservation did not affect the post-thaw stability of cryopreserved PBSC samples.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"73 4","pages":"655-672"},"PeriodicalIF":2.8,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039347","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}

引用次数: 0

Beliefs about medicines' association with endocrine therapy adherence in early breast cancer survivors in Croatia. 克罗地亚早期乳腺癌幸存者对药物的信念与坚持内分泌治疗的关系。

IF 2.8 4区医学

Acta Pharmaceutica Pub Date : 2023-12-26 Print Date: 2023-12-01 DOI: 10.2478/acph-2023-0043

Ana Dugonjić Okroša, Tajana Silovski, Natalija Dedić Plavetić, Hrvoje Silovski, Ana Kovačić, Iva Mucalo

{"title":"Beliefs about medicines' association with endocrine therapy adherence in early breast cancer survivors in Croatia.","authors":"Ana Dugonjić Okroša, Tajana Silovski, Natalija Dedić Plavetić, Hrvoje Silovski, Ana Kovačić, Iva Mucalo","doi":"10.2478/acph-2023-0043","DOIUrl":"10.2478/acph-2023-0043","url":null,"abstract":"This observational, cross-sectional study conducted at the University Hospital Centre Zagreb (UHC Zagreb) aimed to explore patients' beliefs about adjuvant endocrine therapy (AET) as well as their association with non-adherence and sociodemographic and clinical factors. Out of 420 early breast cancer (BC) patients included in the study, 79.5 % perceived AET necessary and important for their health, as measured by the Belief About Medicines Questionnaire (BMQ), with the mean necessity score (20.4 ± 3.68) significantly higher than the mean concerns score (13 ± 4.81) (p < 0.001). Based on the Medication Adherence Report Scale (MARS-5), 44.4 % (n = 182) of the participants were non-adherers, out of which 63.2 % (n = 115) were unintentional and 36.8 % (n = 67) intentional non-adherers. Significantly higher concern beliefs were found among patients that were younger (p < 0.001), employed (p < 0.001), intentionally non-adherent to AET (p = 0.006), had a lower body-mass index (p = 0.005) and a higher level of education (p < 0.001), were premenopausal at the time of diagnosis (p < 0.001), taking tamoxifen treatment (p = 0.05) and receiving ovarian suppression (p < 0.001). Younger patients should be recognized as being at risk of non-adherence as they hold greater concern beliefs about medicines.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"73 4","pages":"673-689"},"PeriodicalIF":2.8,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039336","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}

引用次数: 0

Synthesis, antiproliferative and antiplasmodial evaluation of new chloroquine and mefloquine-based harmiquins. 以氯喹和甲氟喹为基础的新型喹螨醚的合成、抗增殖性和抗疟性评价。

IF 2.8 4区医学

Acta Pharmaceutica Pub Date : 2023-12-26 Print Date: 2023-12-01 DOI: 10.2478/acph-2023-0035

Kristina Pavić, Goran Poje, Lais Pessanha De Carvalho, Jana Held, Zrinka Rajić

{"title":"Synthesis, antiproliferative and antiplasmodial evaluation of new chloroquine and mefloquine-based harmiquins.","authors":"Kristina Pavić, Goran Poje, Lais Pessanha De Carvalho, Jana Held, Zrinka Rajić","doi":"10.2478/acph-2023-0035","DOIUrl":"10.2478/acph-2023-0035","url":null,"abstract":"Here we present the synthesis and evaluation of the biological activity of new hybrid compounds, ureido-type (UT) harmiquins, based on chloroquine (CQ) or mefloquine (MQ) scaffolds and β-carboline alkaloid harmine against cancer cell lines and Plasmodium falciparum. The hybrids were prepared from the corresponding amines by 1,1'-carbonyldiimidazole (CDI)-mediated synthesis. In vitro evaluation of the biological activity of the title compounds revealed two hit compounds. Testing of the antiproliferative activity of the new UT harmiquins, and previously prepared triazole-(TT) and amide-type (AT) CQ-based harmiquins, against a panel of human cell lines, revealed TT harmiquine 16 as the most promising compound, as it showed pronounced and selective activity against the tumor cell line HepG2 (IC 50 = 5.48 ± 3.35 μmol L-1). Screening of the antiplasmodial activities of UT harmiquins against erythrocytic stages of the Plasmodium life cycle identified CQ-based UT harmiquine 12 as a novel antiplasmodial hit because it displayed low IC 50 values in the submicromolar range against CQ-sensitive and resistant strains (IC 50 0.06 ± 0.01, and 0.19 ± 0.02 μmol L-1, respectively), and exhibited high selectivity against Plasmodium, compared to mammalian cells (SI = 92).","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"73 4","pages":"537-558"},"PeriodicalIF":2.8,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039346","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}

引用次数: 0