Acta Pharmaceutica最新文献

Unveiling the antiglioblastoma potential of harmicens, harmine and ferrocene hybrids. 揭示蒿甲素、蒿乙素和二茂铁混合物的抗胶质母细胞瘤潜力。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2024-11-19 DOI: 10.2478/acph-2024-0033

Goran Poje, Davor Šakić, Marina Marinović, Jiangyang You, Michael Tarpley, Kevin P Williams, Nikolina Golub, Jaka Dernovšek, Tihomir Tomašič, Erim Bešić, Zrinka Rajić

{"title":"Unveiling the antiglioblastoma potential of harmicens, harmine and ferrocene hybrids.","authors":"Goran Poje, Davor Šakić, Marina Marinović, Jiangyang You, Michael Tarpley, Kevin P Williams, Nikolina Golub, Jaka Dernovšek, Tihomir Tomašič, Erim Bešić, Zrinka Rajić","doi":"10.2478/acph-2024-0033","DOIUrl":"10.2478/acph-2024-0033","url":null,"abstract":"The poor prognosis of glioblastoma multiforme, inadequate treatment options, and growing drug resistance urge the need to find new effective agents. Due to the significant anti-cancer potential of harmicens, hybrid compounds which comprise harmine/β-carboline and ferrocene moiety, we investigated their antiglioblastoma potential in vitro and mechanism of action (inhibition of DYRK1A, Hsp90, anti-oxidative activity). The results have shown that triazole-type harmicens, namely 5, with a ferrocene moiety in C-3 position of the β-carboline ring (IC 50 = 3.7 ± 0.1 µmol L-1, SI = 12.6) and 9, the C-6 substituted harmicene (IC 50 = 7.4 ± 0.5 µmol L-1, SI = 5.8) exert remarkable activity and selectivity against human malignant glioblastoma cell line (U251) in vitro. On the other hand, amide-type harmicens 10, 12, and 14 exhibited strong, but non-selective activity, in the low micro-molar range. Mechanistic studies revealed that among active compounds, amide-type harmicens 12 and 14 inhibit DYRK1A and Hsp90 CTD, whereas compound 14 showed pronounced antioxidative activity. Therefore, the antiproliferative activity of harmicens might be a combination of complex molecular interactions.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666830","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

Phenolic content and antioxidant activity of Croatian and German honey. 克罗地亚和德国蜂蜜的酚含量和抗氧化活性。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2024-11-19 DOI: 10.2478/acph-2024-0031

Valerija Vujčić Bok, Ivana Šola, Gordana Rusak, Alan Budisavljević, Rosa Nguyen, Jutta Ludwig-Müller, Željan Maleš

{"title":"Phenolic content and antioxidant activity of Croatian and German honey.","authors":"Valerija Vujčić Bok, Ivana Šola, Gordana Rusak, Alan Budisavljević, Rosa Nguyen, Jutta Ludwig-Müller, Željan Maleš","doi":"10.2478/acph-2024-0031","DOIUrl":"10.2478/acph-2024-0031","url":null,"abstract":"Since honey has a therapeutic role in the treatment of many diseases, we investigated the content of phenolic compounds and the antioxidant activity in acacia (Robinia pseudoacacia L.), chestnut (Castanea sativa Mill.) and lime-tree (Tilia spp.) honey originating from Croatia and Germany. Total phenols, flavonols, and flavanols contents were observed at higher levels in Croatian Castanea honey compared to German Castanea honey. Significant higher values of total flavanols and hydroxycinnamic acids were measured in Croatian Tilia honey compared to German Tilia honey. For Robinia honey, significantly higher values of total phenols and flavonols were observed in almost all Croatian honey samples compared to German honey. Croatian honey samples had higher antioxidant activity compared to German honey samples with most tested methods. The highest total phenols, total flavanols, ABTS, DPPH, and FRAP values were measured in Castanea honey, then in Robinia honey, and the lowest values in Tilia honey samples. With new developed HPLC method, pinobanksin, pinocembrin, and chrysin were identified in the majority of honey samples. Our results imply that both botanical and geographical origin influence the final quality of phenolic compounds and antioxidant activity in honey. A high positive correlation between the results of antioxidant activity and polyphenols was detected.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666828","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

Light-induced rearrangement from macrocyclic to bicyclic lactam: A case study of N-chlorinated laurolactam. 从大环内酰胺到双环内酰胺的光诱导重排：N-chlorinated laurolactam 的案例研究。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2024-11-19 DOI: 10.2478/acph-2024-0035

Gabrijel Zubčić, Kristina Pavić, Jiangyang You, Valerije Vrček, Tomislav Portada, Erim Bešić, Davor Šakić

{"title":"Light-induced rearrangement from macrocyclic to bicyclic lactam: A case study of N-chlorinated laurolactam.","authors":"Gabrijel Zubčić, Kristina Pavić, Jiangyang You, Valerije Vrček, Tomislav Portada, Erim Bešić, Davor Šakić","doi":"10.2478/acph-2024-0035","DOIUrl":"10.2478/acph-2024-0035","url":null,"abstract":"Converting macrocycle lactams into bicyclic lactams is proposed as an additional way to further increase the metabolic stability of peptide-based drugs. Unfortunately, the synthesis of bicyclic lactams has to start almost from scratch. This study explores the Hofmann-Löffler-Freytag (HLF) reaction mechanism and products as a potential late-stage functionalisation strategy for facile conversion of macrocyclic to bicyclic ring. Laurolactam, a macrocyclic amide, exhibits significant potential for transformation into bioactive bicyclic structures with smaller, β-, γ-, δ-, and ε-lactam rings, further increasing rigidity and hydrolytic stability. With irradiation provided by a 370 nm lamp, light-induced rearrangement reaction was monitored using nuclear magnetic resonance (NMR), while involved radical intermediates were trapped using N-tert-butyl-α-phenylnitrone (PBN) spin-trap and characterised via EPR. While only two radical adduct types were identified in the electron para magnetic resonance (EPR) (C-centered radical and chlorine radical), all eight possible products are observed in the NMR. Quantum chemical calculations provide deeper insights into reaction thermodynamics and kinetics, explaining why the N-centered radical was not observed. This research highlights the feasibility of using the HLF reaction to transform macrocyclic lactams into stable bicyclic drug candidates, paving the way for new therapeutic developments.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666827","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

Fall risk-increasing drugs and associated health outcomes among community-dwelling older patients: A cross-sectional study in Croatian cohort of the EuroAgeism H2020 project. 在社区居住的老年患者中，增加跌倒风险的药物和相关健康结果：欧洲老龄化 H2020 项目克罗地亚队列横断面研究。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2024-11-19 DOI: 10.2478/acph-2024-0034

Elizabeta Paar, Eleonora De Lai, Margita Držaić, Ingrid Kummer, Iva Bužančić, Maja Ortner Hadžiabdić, Jovana Brkic, Daniela Fialová

{"title":"Fall risk-increasing drugs and associated health outcomes among community-dwelling older patients: A cross-sectional study in Croatian cohort of the EuroAgeism H2020 project.","authors":"Elizabeta Paar, Eleonora De Lai, Margita Držaić, Ingrid Kummer, Iva Bužančić, Maja Ortner Hadžiabdić, Jovana Brkic, Daniela Fialová","doi":"10.2478/acph-2024-0034","DOIUrl":"10.2478/acph-2024-0034","url":null,"abstract":"Our study aimed to assess the prevalence of fall risk-increasing drugs (FRIDs) in a sample of community-residing older patients in Croatia and its association with negative health outcomes. An observational, cross-sectional study was conducted on older patients (65+) visiting community pharmacies in three regionally different study sites in Croatia. Data were collected using a questionnaire developed for that purpose and included components of comprehensive geriatric assessment. Prevalence of FRIDs was identified using the \"Screening Tool of Older Persons Prescriptions in older adults with high fall risk\" (STOPPFall). In the sample of 407 participants (median age 73 (IQR 69-70) years; 63.9 % females), 79.1 % used at least one FRID. The most common drug classes were diuretics, benzodiazepines, and opioids (in 51.1 %, 38.1 %, and 17.2 % participants, respectively). More FRIDs were prescribed to the oldest old patients (85+) and participants from poorer regions of Croatia (Slavonia) (p < 0.05). Exposition to FRIDs was identified as the significant risk factor associated with falls (OR = 1.24 (1.04-1.50); p = 0.020) and higher health-care utilization (OR = 1.29 (1.10-1.51); p = 0.001). Our study highlights the need for rationalization of FRID use. To reduce the unnecessary exposure to FRIDs in older adults, health-care professionals must consider high individualization of medication schemes regarding selection, dosing, and combinations of only necessary FRIDs.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666826","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

Total phenolic content, flavonoid content and antioxidant potential of Petasites hybridus and related species from Croatia and considerations regarding their pharmaceutical significance. 克罗地亚杂交矮牵牛及相关物种的总酚含量、类黄酮含量和抗氧化潜力，以及对其制药意义的考虑。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2024-11-19 DOI: 10.2478/acph-2024-0032

Maja Friščić, Katarina Vilić, Sandra Jurić, Kroata Hazler Pilepić, Željan Maleš

{"title":"Total phenolic content, flavonoid content and antioxidant potential of Petasites hybridus and related species from Croatia and considerations regarding their pharmaceutical significance.","authors":"Maja Friščić, Katarina Vilić, Sandra Jurić, Kroata Hazler Pilepić, Željan Maleš","doi":"10.2478/acph-2024-0032","DOIUrl":"10.2478/acph-2024-0032","url":null,"abstract":"Extracts obtained from common butterbur (Petasites hybridus), standardized to petasins, are existing pharmaceutical options for the treatment and/or prevention of allergic rhinitis (leaves) and migraine (rhizomes). In this study, the total phenolic content, flavonoid content, and antioxidant potential of ten samples of Croatian Petasites species (four P. hybridus, four P. albus, one P. kabli kianus, and one P. paradoxus) obtained by ultrasound-assisted extraction of leaves were compared. The total phenolic content (Folin-Ciocalteu assay) of methanolic leaf extracts ranged from 4.43 ± 0.09 to 10.76 ± 0.60 mg gallic acid equivalent g-1 dry mass (mg GAE g-1 DM) for P. hybridus and from 6.66 ± 0.43 to 19.92 ± 2.90 mg GAE g-1 DM for P. albus samples, while those of P. kablikianus and P. paradoxus were equal to 7.56 ± 0.17 mg GAE g-1 DM and 10.22 ± 0.46 mg GAE g-1 DM, respectively. Flavonoid content (AlCl3 assay) varied between 2.51 ± 0.10 and 4.03 ± 0.08 mg quercetin equivalent g-1 dry mass (mg QE g-1 DM) for P. hybridus and between 2.21 ± 0.09 and 5.22 ± 0.02 mg QE g-1 DM for P. albus samples, while those of P. kablikianus and P. paradoxus were equal to 5.59 ± 0.05 mg QE g-1 DM and 5.50 ± 0.09 mg QE g-1 DM, respectively. Antioxidant potential was in high correlation with total phenolic content (r = 0.93, p < 0.001). Due to the expected contribution of plant polyphenols and flavonoids to the activity of butterbur extracts and their observed great variabilities, determining the content of these compounds may be of interest to the pharmaceutical industry.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666829","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

Complete blood count parameters and inflammation-related biomarkers in patients with colorectal carcinoma. 结直肠癌患者的全血细胞计数参数和炎症相关生物标记物。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2024-11-19 DOI: 10.2478/acph-2024-0036

Martha Koržinek, Ivana Ćelap, Marija Fabijanec, Tena Žanić, Neven Ljubičić, Neven Baršić, Donatella Verbanac, Karmela Barišić, Marija Grdić Rajković

{"title":"Complete blood count parameters and inflammation-related biomarkers in patients with colorectal carcinoma.","authors":"Martha Koržinek, Ivana Ćelap, Marija Fabijanec, Tena Žanić, Neven Ljubičić, Neven Baršić, Donatella Verbanac, Karmela Barišić, Marija Grdić Rajković","doi":"10.2478/acph-2024-0036","DOIUrl":"10.2478/acph-2024-0036","url":null,"abstract":"The aim of this study was to determine whether there are differences in complete blood count parameters (CBC) and inflammation-related biomarkers, MPV/PC, PLR, NLR, LWR, LMR, NMR, and LCR, among patients with colorectal carcinoma (CRC) and patients with colorectal adenomas. The study included 155 patients who were divided into two groups according to histopathological analysis - 74 adenomas patients and 81 CRC patients. A routine examination of CBC was conducted on Sysmex XN1000 whereas CRP was measured on Alinity ci-series. Statistical analysis was performed by ROC curve analysis using MedCalc Statistical Software. In CRC patients, hemoglobin concentration, hematocrit, MCV, MCH, and MCHC were lower, while RDW was higher (p < 0.001), compared to patients with adenomas. Total leukocyte count (p = 0 .006), absolute neutrophils (p = 0.005), and absolute monocytes (p = 0.007) were lower while relative eosinophils (p = 0.001) and relative basophils (p = 0.001) were higher in CRC patients. Platelet count (p < 0.001) was significantly higher and MPV (p = 0.003) was significantly lower in CRC patients. Furthermore, MPV/PC (p < 0.001) was significantly lower and PLR (p < 0.001) was significantly higher in CRC. Moreover, Receiver Operating Characteristic (ROC) analysis revealed poor diagnostic accuracy, for all tested parameters (AUC was 0.7 or less). PC, MPV, MPV/PC, and PLR were significantly different between study groups, but ROC analysis revealed poor diagnostic accuracy. Lower hemo globin levels in CRC patients are possibly due to more frequent and excessive bleeding. Higher levels of basophils and eosinophils in CRC patients are indicators of inflammatory reaction, which is linked to CRC.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666825","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

Tannic acid elicits differential gene regulation in prostate cancer apoptosis. 单宁酸在前列腺癌凋亡过程中引发不同的基因调控。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2024-09-14 Print Date: 2024-09-01 DOI: 10.2478/acph-2024-0020

Sinan Kandir, Sevtap Karakurt, Çiğdem Gökçek-Saraç, Serdar Karakurt

{"title":"Tannic acid elicits differential gene regulation in prostate cancer apoptosis.","authors":"Sinan Kandir, Sevtap Karakurt, Çiğdem Gökçek-Saraç, Serdar Karakurt","doi":"10.2478/acph-2024-0020","DOIUrl":"https://doi.org/10.2478/acph-2024-0020","url":null,"abstract":"Prostate cancer is a significant global health concern that requires innovative therapeutic investigations. Here, the potential anticancer properties of tannic acid were evaluated by examining its effects on apoptosis in prostate cancer cell lines. PC-3 and LnCaP prostate adeno carcinoma cells, along with PNT1A prostate control cells, were cultured and divided into untreated and tannic acid-treated groups. Cell proliferation, cytotoxicity, and effects of tannic acid on the cell death mechanism were evaluated. mRNA expression levels of 84 genes were explored in cells following tannic acid treatment. Notably, tannic acid-induced down-regulation of several pro-survival genes, including ATM, BCL2, BCL2A1, BIK, BIRC2, BIRC3, BRE, CASP3, CASP6, CASP8, CHEK2, CRADD, PPIA, RPA3, TNFSF18, TRAF1, TRAF2, TRAF4, and TRAF5 in both cell lines. Moreover, tannic acid treatment led to the up-regulation of various pro-apoptotic genes, such as BCL10, BIRC3, BNIP3, CASP1, CASP5, CD40, CIDEB, DAPK2, FASLG, GADD45A, MYD88, RPA 3, TNFRSF10D, TNFRSF17, TNFRSF8, TNFSF13B, TNFSF4, TNFSF7, TNFSF8, TNFSF9, TP53, TRAF1, and TRAF2 in both PC-3 and LnCap cells. These findings highlight tannic acid's ability to induce apoptosis in prostate cancer cells through pro-apoptotic pathways. This study concludes that tannic acid selectively inhibits prostate cancer cell growth.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"539-550"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278658","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 tyrosine kinase inhibitor lenvatinib is oxidized by rat cytochromes P450 and affects their expression in rat liver. 酪氨酸激酶抑制剂来伐替尼被大鼠细胞色素P450氧化，并影响它们在大鼠肝脏中的表达。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2024-09-14 Print Date: 2024-09-01 DOI: 10.2478/acph-2024-0027

Radek Indra, Sandra Jelínková, Katarína Kollárová, Petra Zahumenská, Josef Dvořák, Šárka Dušková, Helena Dračínská

{"title":"The tyrosine kinase inhibitor lenvatinib is oxidized by rat cytochromes P450 and affects their expression in rat liver.","authors":"Radek Indra, Sandra Jelínková, Katarína Kollárová, Petra Zahumenská, Josef Dvořák, Šárka Dušková, Helena Dračínská","doi":"10.2478/acph-2024-0027","DOIUrl":"https://doi.org/10.2478/acph-2024-0027","url":null,"abstract":"Lenvatinib is an orally effective tyrosine kinase inhibitor used to treat several types of tumors, including progressive, radioiodine-refractory differentiated thyroid cancer and advanced renal cell carcinoma. Although this drug is increasingly used in therapy, its metabolism and effects on the organism are still not described in detail. Using the rat as an experimental animal model, this study aimed to investigate the metabolism of lenvatinib by rat microsomal enzymes and cytochrome P450 (CYPs) enzymes recombinantly expressed in SupersomesTM in vitro and to assess the effect of lenvatinib on rat CYP expression in vivo. Two metabolites, O-desmethyl lenvatinib, and lenvatinib N-oxide, were produced by rat CYPs in vitro. CYP2A1 and 2C12 were found to be the most effective in forming O-desmethyl lenvatinib, while CYP3A2 was found to primarily form lenvatinib N-oxide. The administration of lenvatinib to rats caused changes in the expression of mRNA and protein, as well as the activity of various CYPs, particularly in an increase in CYP1A1. Thus, the administration of lenvatinib to rats has an impact on the level of CYPs.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"441-459"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278659","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

PPIA, HRPT1, and PGK1 genes as the appropriate combination for RT-qPCR normalization in alveolar and femoral bone remodeling in olanzapine-treated rats. 将 PPIA、HRPT1 和 PGK1 基因作为奥氮平治疗大鼠牙槽骨和股骨头重塑中 RT-qPCR 正常化的适当组合。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2024-09-14 Print Date: 2024-09-01 DOI: 10.2478/acph-2024-0029

Saranda Disha-Ibrahimi, Gorazd Drevenšek, Martina Drevenšek, Janja Marc, Irena Prodan Žitnik

{"title":"PPIA, HRPT1, and PGK1 genes as the appropriate combination for RT-qPCR normalization in alveolar and femoral bone remodeling in olanzapine-treated rats.","authors":"Saranda Disha-Ibrahimi, Gorazd Drevenšek, Martina Drevenšek, Janja Marc, Irena Prodan Žitnik","doi":"10.2478/acph-2024-0029","DOIUrl":"https://doi.org/10.2478/acph-2024-0029","url":null,"abstract":"Reliable gene expression analysis in bone remodeling studies requires an appropriate selection of internal controls, i.e. stable reference genes for the normalization of quantitative real-time PCR (RT-qPCR), the most common method used for quantifying gene expression measurements. Even the most widely used reference genes can have variable expression under different experimental conditions, or in different tissue types or treatment regimes, so selecting appropriate controls is a key step in ensuring reliable results. The aim of this research was to identify the most stable reference gene(s) for the study of olanzapine modulated bone remodeling in rats. RNA was isolated from the maxillary alveolar and femoral bones of olanzapine or placebo-treated Wistar rats and transcribed to cDNA. The expression of 12 candidate reference genes was assessed by RT-qPCR. Their expressions were analysed using GeNorm, NormFinder, BestKeeper and delta Ct algorithms, and by the comprehensive ranking method. PPIA, HRPT1 and PGK1 were the most stably expres sed reference genes and the combination of the three genes was optimal for normalization. This study is the first to identify the optimal reference genes for research in olanzapine-exposed rats, which serve as a pivotal benchmark for enhancing the accuracy and reliability of future RT-qPCR expression in bone studies.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"511-524"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278656","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 and biochemical evaluation of new 3-amido-4-substituted monocyclic ß-lactams as inhibitors of penicillin-binding protein(s). 作为青霉素结合蛋白抑制剂的新型 3-氨基-4-取代单环 ß-内酰胺的合成与生化评估。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2024-09-14 Print Date: 2024-09-01 DOI: 10.2478/acph-2024-0024

Katarina Grabrijan, Nika Strašek Benedik, Alen Krajnc, Krištof Bozovičar, Damijan Knez, Matic Proj, Irena Zdovc, Izidor Sosič, Carlos Contreras-Martel, Andréa Dessen, Martina Hrast Rambaher, Stanislav Gobec

{"title":"Synthesis and biochemical evaluation of new 3-amido-4-substituted monocyclic ß-lactams as inhibitors of penicillin-binding protein(s).","authors":"Katarina Grabrijan, Nika Strašek Benedik, Alen Krajnc, Krištof Bozovičar, Damijan Knez, Matic Proj, Irena Zdovc, Izidor Sosič, Carlos Contreras-Martel, Andréa Dessen, Martina Hrast Rambaher, Stanislav Gobec","doi":"10.2478/acph-2024-0024","DOIUrl":"https://doi.org/10.2478/acph-2024-0024","url":null,"abstract":"In the final phases of bacterial cell wall synthesis, penicillin-binding proteins (PBPs) catalyze the cross-linking of peptidoglycan. For many decades, effective and non-toxic β-lactam antibiotics have been successfully used as mimetics of the d-Ala-d-Ala moiety of the natural substrate and employed as irreversible inhibitors of PBPs. In the years following their discovery, the emergence of resistant bacteria led to a decline in their clinical efficacy. Using Staudinger cycloaddition, we synthesized a focused library of novel monocyclic β-lactams in which different substituents were introduced at the C4 position of the β-lactam ring, at the C3 amino position, and at the N1 lactam nitrogen. In biochemical assays, the compounds were evaluated for their inhibitory effect on the model enzyme PBP1b from Streptococcus pneumoniae. Upon investigation of the antibacterial activity of the newly prepared compounds against ESKAPE pathogens, some compounds showed moderate inhibition. We also examined their reactivity and selectivity in a biochemical assay with other enzymes that have a catalytic serine in the active site, such as human cholinesterases, where they also showed no inhibitory activity, highlighting their specificity for bacterial targets. These compounds form the basis for further work on new monocyclic β-lactams with improved antibacterial activity.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"423-440"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278657","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