rss_2.0Acta Pharmaceutica FeedSciendo RSS Feed for Acta Pharmaceuticahttps://sciendo.com/journal/ACPHhttps://www.sciendo.comActa Pharmaceutica 's Coverhttps://sciendo-parsed-data-feed.s3.eu-central-1.amazonaws.com/612ea2b21000020b549d6257/cover-image.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20211021T072603Z&X-Amz-SignedHeaders=host&X-Amz-Expires=604800&X-Amz-Credential=AKIA6AP2G7AKDOZOEZ7H%2F20211021%2Feu-central-1%2Fs3%2Faws4_request&X-Amz-Signature=bad8d507a9fe108db55e40124cceeec8604bc35773e973cff51818359e4b1504200300Design, synthesis and molecular modeling study of substituted indoline-2-ones and spiro[indole-heterocycles] with potential activity against Gram-positive bacteriahttps://sciendo.com/article/10.2478/acph-2022-0004<abstract> <title style='display:none'>Abstract</title> <p>Longstanding and firsthand infectious diseases are challenging community health threats. A new series of isatin derivatives bearing β-hydroxy ketone, chalcone, or spiro-heterocycle moiety, was synthesized in a good yield. Chemical structures of the synthesized compounds were elucidated using spectroscopic techniques and elemental analysis. Antibacterial activities of the compounds were then evaluated <italic>in vitro</italic> and by <italic>in silico</italic> modeling. The compounds were more active against Gram-positive bacteria, <italic>Staphylococcus aureus</italic> (<italic>MIC</italic> = 0.026–0.226 mmol L<sup>−1</sup>) and <italic>Bacillus subtilis</italic> (<italic>MIC</italic> = 0.348–1.723 mmol L–1) than against Gram-negative bacteria (<italic>MIC</italic> = 0.817–7.393 mmol L<sup>–1</sup>). Only 3-hydroxy-3-(2-(2,5-dimethylthiophen-3-yl)-2-oxoethyl)indolin-2-one (<bold>1b</bold>) was found as active as imipenem against <italic>S. aureus</italic> (<italic>MIC</italic> = 0.026 mmol L<sup>–1</sup>). <italic>In silico</italic> docking of the compounds in the binding sites of a homology modeled structure of <italic>S. aureus</italic> histidine kinase-Walk allowed us to shed light on the binding mode of these novel inhibitors. The highest antibacterial activity of <bold>1b</bold> is consistent with its highest docking score values against <italic>S. aureus</italic> histidine kinase.</p> </abstract>ARTICLE2021-08-30T00:00:00.000+00:00Application of neurotoxin- and pesticide-induced animal models of Parkinson’s disease in the evaluation of new drug delivery systemshttps://sciendo.com/article/10.2478/acph-2022-0008<abstract> <title style='display:none'>Abstract</title> <p>Parkinson’s disease (PD) is the second most prevalent neuro-degenerative disease after Alzheimer´s disease. It is characterized by motor symptoms such as akinesia, bradykinesia, tremor, rigidity, and postural abnormalities, due to the loss of nigral dopaminergic neurons and a decrease in the dopa-mine contents of the caudate-putamen structures. To this date, there is no cure for the disease and available treatments are aimed at controlling the symptoms. Therefore, there is an unmet need for new treatments for PD. In the past decades, animal models of PD have been proven to be valuable tools in elucidating the nature of the pathogenic processes involved in the disease, and in designing new pharmacological approaches. Here, we review the use of neurotoxin-induced and pesticide-induced animal models of PD, specifically those induced by rotenone, paraquat, maneb, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and 6-OHDA (6-hydroxydopamine), and their application in the development of new drug delivery systems for PD.</p> </abstract>ARTICLE2021-08-30T00:00:00.000+00:00Molecular networking-assisted flavonoid profile of extract in relation to its protective effects on carbon tetrachloride-induced hepatorenal damage in ratshttps://sciendo.com/article/10.2478/acph-2022-0009<abstract> <title style='display:none'>Abstract</title> <p>The aim of the study was to provide an in-depth characterization of the methanol-aqueous extract from the aerial parts of <italic>Gypsophila glomerata</italic> Pall. Ex Adams (Caryophyllaceae) (EGG) and to assess its protective potential on carbon tetrachloride (CCl<sub>4</sub>)-induced liver and kidney damage in male Wistar rats. Twenty-two flavonoid <italic>C-</italic>, <italic>O</italic>- and <italic>C,O</italic>--glycosides in EGG were annotated by mass spectrometry--based molecular networking; nine of them are reported in this species for the first time. Fourteen-day oral administration of EGG at a dose 200 mg kg<sup>−1</sup> bm prevented significantly CCl<sub>4</sub>-induced liver injury, discerned by an amelioration of the markers of oxidative stress (GSH and MDA) and transaminase activity. EGG decreased the serum level of urea and creatinine as well. The observed improvement of biochemical parameters was supported by histopathological observations. The protective hepatorenal effects of EGG, rich in 2“-<italic>О</italic>-pentosyl-6-<italic>С</italic>-hexosyl-apigenin/luteolin/ methylluteolin and their acetyl- and methoxycinnamoyl-derivatives, were comparable with the effects of the positive control silymarin.</p> </abstract>ARTICLE2021-08-30T00:00:00.000+00:00Neuroprotective effects of arbutin against oxygen and glucose deprivation-induced oxidative stress and neuroinflammation in rat cortical neuronshttps://sciendo.com/article/10.2478/acph-2022-0002<abstract> <title style='display:none'>Abstract</title> <p>In this study, the neuroprotective potential of arbutin (100 µmol L<sup>−1</sup>) pre-treatment and post-treatment against oxygen/ glucose deprivation (OGD) and reoxygenation (R) induced ischemic injury in cultured rat cortical neurons was explored. The OGD (60 min) and reoxygenation (24 h) treatment significantly (<italic>p</italic> &lt; 0.001) compromised the antioxidant defence in cultured neurons. Subsequently, an increase (<italic>p</italic> &lt; 0.001) in lipid peroxidation and inflammatory cytokines (tumour necrosis factor-α and nuclear factor kappa-B) declined neuron survival. In pre- and post-condition experiments, treatment with arbutin enhanced both survival (<italic>p</italic> &lt; 0.01) and integrity (<italic>p</italic> &lt; 0.05) of cultured neurons. Results showed that arbutin protects (<italic>p</italic> &lt; 0.05) against peroxidative changes, inflammation, and enhanced the antioxidant activity (<italic>e.g.,</italic> glutathione, superoxide dismutase and catalase) in cultured neurons subjected to OGD/R. It can be inferred that arbutin could protect against ischemic injuries and stroke. The anti-ischemic activity of arbutin can arrest post-stroke damage to the brain.</p> </abstract>ARTICLE2021-08-30T00:00:00.000+00:00Optimizing glycerosome formulations an orthogonal experimental design to enhance transdermal triptolide deliveryhttps://sciendo.com/article/10.2478/acph-2022-0006<abstract> <title style='display:none'>Abstract</title> <p>Triptolide exerts strong anti-inflammatory and immunomodulatory effects; however, its oral administration might be associated with side effects. Transdermal administration can improve the safety of triptolide. In this study, glycerosomes were prepared as the transdermal vehicle to enhance the transdermal delivery of triptolide. With entrapment efficiency and drug loading as dependent variables, the glycerosome formulation was optimized using an orthogonal experimental design. Phospholipid-to-cholesterol and phospholipid-to-triptolide mass ratios of 30:1 and 5:1, respectively and a glycerol concentration of 20 % (<italic>V/V</italic>) were used in the optimization. The glycerosomes prepared with the optimized formulation showed good stability, with an average particle size of 153.10 ± 2.69 nm, a zeta potential of –45.73 ± 0.60 mV and an entrapment greater than 75 %. Glycerosomes significantly increased the transdermal delivery of triptolide compared to conventional liposomes. As efficient carriers for the transdermal delivery of drugs, glycerosomes can potentially be used as an alternative to oral triptolide administration.</p> </abstract>ARTICLE2021-08-30T00:00:00.000+00:00Knockdown of Annexin A1 induces apoptosis, causing G2/M arrest and facilitating phagocytosis activity in human leukemia cell lineshttps://sciendo.com/article/10.2478/acph-2022-0005<abstract> <title style='display:none'>Abstract</title> <p>Annexin A1 (ANXA1) is an endogenous protein involved in the control of proliferation, cell cycle, phagocytosis, and apoptosis in several types of cancer. To investigate the effects of ANXA1 knockdown in leukemia cells, transfection with specific ANXA1 siRNA was performed. Cell cycle and apoptosis were analyzed using flow cytometry and a mechanism involving caspases and Bcl-2 was quantified using Western blotting. Phagocytosis activity was evaluated using hematoxylin &amp; eosin staining. The ANXA1 expression was significantly downregulated after the knockdown and apoptosis was induced in tested cells. The expression of caspase-9 and -3 increased in U937 and Jurkat cells respectively. Bcl-2 expression was downregulated in K562 and Jurkat cells while upregulated in U937. The number of leukemic cells arrested at the G2/M phase and the phagocytosis index were significantly increased in transfected cells. This suggests that ANXA1 knockdown might be a potential approach in the therapeutic strategy for leukemia.</p> </abstract>ARTICLE2021-08-30T00:00:00.000+00:00Initiation of insulin therapy in patients with type 2 diabetes: An observational studyhttps://sciendo.com/article/10.2478/acph-2022-0011<abstract> <title style='display:none'>Abstract</title> <p>The aim of the study was to assess the initiation of insulin therapy in patients with type 2 diabetes using health claims data on prescription medicines. The study evaluated time to insulin initiation and prescribing patterns of other anti-diabetic medicines before and after insulin initiation. Five years after starting non-insulin antidiabetic therapy, 6.4 % of patients were prescribed insulin, which is substantially lower compared to other similar studies. Among all patients who initiated insulin therapy in 2013, 30 % did not continue any other antidiabetic therapy. However, this proportion was lowered to 20 % in 2018. Before insulin initiation in 2018, metformin was prescribed in only 67 % of patients and sulfonylureas in 78 % of patients. Moreover, metformin and sulfonylureas were discontinued after insulin initiation in 26 and 37 % of patients, resp. More attention should be paid to the continuation of oral anti-diabetics, particularly metformin, after insulin initiation.</p> </abstract>ARTICLE2021-08-30T00:00:00.000+00:00Update on glasdegib in acute myeloid leukemia – broadening horizons of Hedgehog pathway inhibitorshttps://sciendo.com/article/10.2478/acph-2022-0007<abstract> <title style='display:none'>Abstract</title> <p>Numerous new emerging therapies, including oral targeted chemotherapies, have recently entered the therapeutic arsenal against acute myeloid leukemia (AML). The significant shift toward the use of these novel therapeutics, administered either alone or in combination with intensive or low-intensity chemotherapy, changes the prospects for the control of this disease, especially for elderly patients. Glasdegib, an oral Hedgehog pathway inhibitor, showed satisfactory response rates associated with moderate toxicity and less early mortality than standard induction regimens in this population. It was approved in November 2018 by the FDA and in June 2020 by the EMA for use in combination with low-dose cytarabine as a treatment of newly-diagnosed AML in patients aged ≥ 75 and/or unfit for intensive induction chemotherapy. The current paper proposes an extensive, up-to-date review of the preclinical and clinical development of glasdegib. Elements of its routine clinical use and the landscape of ongoing clinical trials are also stated.</p> </abstract>ARTICLE2021-08-30T00:00:00.000+00:00UPLC-HRESI-MS and GC-MS analysis of the leaves of https://sciendo.com/article/10.2478/acph-2022-0001<abstract> <title style='display:none'>Abstract</title> <p>The alkaloid-rich fraction obtained by fractionation of the crude methanolic extract of the leaves of wild tobacco tree <italic>Nicotiana glauca</italic> Graham (Solanaceae) was analyzed using UPLC-MS and GC-MS. Anabasine, a piperidine alkaloid, was identified as the major constituent with approximately 60 % (<italic>m</italic>/<italic>m</italic>) of the alkaloid-rich fraction. In addition to anabasine, six secondary metabolites were identified using high-resolution UPLC-MS. Anabasine was quantified in the leaves to be 1 mg g<sup>−1</sup> dry plant material. The GC-MS analysis revealed five compounds with anabasine as the major component, while nicotine was not detected. Moreover, GC-MS was used for the analysis of the volatile oil that was obtained by hydro-distillation from the leaves of <italic>N. glauca</italic>. The volatile plant oil was found to be rich in oxygenated sesquiterpenes (<italic>e.g</italic>., <italic>β</italic>-bisabolol) and carboxylic acids and esters (<italic>e.g</italic>., ethyl linoleate and hexadecanoic acid), whereas anabasine was not detected.</p> </abstract>ARTICLE2021-08-30T00:00:00.000+00:00Evaluation of COVID-19 protease and HIV inhibitors interactionshttps://sciendo.com/article/10.2478/acph-2022-0010<abstract> <title style='display:none'>Abstract</title> <p>The epidemic of the novel coronavirus disease (COVID-19) that started in 2019 has evoked an urgent demand for finding new potential therapeutic agents. In this study, we performed a molecular docking of anti-HIV drugs to refine HIV protease inhibitors and nucleotide analogues to target COVID-19. The evaluation was based on docking scores calculated by AutoDock Vina and top binding poses were analyzed. Our results suggested that lopinavir, darunavir, atazanavir, remdesivir, and tipranavir have the best binding affinity for the 3-chymotrypsin-like protease of COVID-19. The comparison of the binding sites of three drugs, namely, darunavir, atazanavir and remdesivir, showed an overlap region of the protein pocket. Our study showed a strong affinity between lopinavir, darunavir, atazanavir, tipranavir and COVID-19 protease. However, their efficacy should be confirmed by <italic>in vitro</italic> studies since there are concerns related to interference with their active sites.</p> </abstract>ARTICLE2021-08-30T00:00:00.000+00:00Determination of penicillamine, tiopronin and glutathione in pharmaceutical formulations by kinetic spectrophotometryhttps://sciendo.com/article/10.2478/acph-2021-0038<abstract><title style='display:none'>Abstract</title><p>A novel and simple method for the determination of penicillamine (PEN), tiopronin (mercaptopropionyl glycine, MPG) and glutathione (GSH) in pharmaceutical formulations by kinetic spectrophotometry has been developed and validated. It is based on the redox reaction where the thiol compound (RSH) reduces Cu<sup>II</sup>-neocuproine complex to Cu<sup>I</sup>-neocuproine complex. The non-steady state signal of the formed Cu<sup>I</sup>- neocuproine complex is measured at 458 nm. The initial rate and fixed time (at 1 min) methods were validated. The calibration graph was linear in the concentration range from 8.0 × 10<sup>‒7</sup> to 8.0 × 10<sup>‒5</sup> mol L<sup>−1</sup> for the initial rate method and from 6.0 × 10<sup>‒7</sup> to 6.0 × 10<sup>−5</sup> mol L<sup>−1</sup> for the fixed time method, with the detection limits of 2.4 × 10<sup>−7</sup> and 1.4 × 10<sup>‒7</sup> mol L<sup>−1</sup>, resp. Levels of PEN, MPG and GSH in pharmaceutical formulations were successfully assayed by both methods. The advantages of the presented methods include sensitivity, short analysis time, ease of application and low cost.</p></abstract>ARTICLE2021-04-03T00:00:00.000+00:00Pinocembrin flavanone inhibits cell viability in PC-3 human prostate cancer by inducing cellular apoptosis, ROS production and cell cycle arresthttps://sciendo.com/article/10.2478/acph-2021-0042<abstract><title style='display:none'>Abstract</title><p>The main purpose of the present study was to evaluate the antitumor effects of pinocembrin in human prostate cancer cells (PC-3) along with investigating its effects on cell apoptosis, endogenous ROS production and cell cycle. MTT assay and clonogenic assays were used to study the effects on cell viability and cancer colony formation, respectively. Fluorescence microscopy along with Western blotting was used to study apoptotic effects induced by pinocembrin. Flow cytometry was used to study effects on ROS production and cell cycle phase distribution. Results indicated that pinocembrin promoted inhibition cell proliferation along with reducing cancer colony formation of PC-3 cells in a dose-dependent manner. Pinocembrin induced regulatory effects over expressions of caspase-3, caspase-9, Bax and Bcl-2, thereby promoting apoptotic cell death in PC-3 cells. It also led to the dose-dependent G0/G1 cell cycle arrest. In conclusion, pinocembrin exhibits strong anticancer effects in human prostate cancer cells mediated <italic>via</italic> apoptosis, endogenous ROS production and G0/G1 cell cycle arrest.</p></abstract>ARTICLE2021-04-03T00:00:00.000+00:00Upregulation of p53 by tannic acid treatment suppresses the proliferation of human colorectal carcinomahttps://sciendo.com/article/10.2478/acph-2021-0036<abstract><title style='display:none'>Abstract</title><p>The present study’s objective is to clarify the molecular mechanisms of tannic acid effects on the viability of human colorectal carcinoma (CRC). Tannic acid is stable for up to 48 h and is localized in both cytoplasm and nucleus. It dose-dependently inhibited the viability of CRC cell lines; SW-620 and HT-29 with <italic>IC</italic><sub>50</sub> values of 7.2 ± 0.8 and 37.6 ± 1.4 µmol L<sup>–1</sup>. Besides, metastatic, invasive, and colony formation properties of CRC cells were significantly inhibited following the tannic acid treatment (<italic>p</italic> &lt; 0.001). Tannic acid has been found to modulate enzyme, protein, and gene expressions of NQO1 in different levels and the upregulation of protein/gene expressions of p53 (<italic>p</italic> &lt; 0.001), which leads the cells to trigger apoptosis. In conclusion, the present <italic>in vitro</italic> study may supply a significant background for <italic>in vivo</italic> studies in which the molecular mechanisms of antioxidant and chemopreventive activities of tannic acid will completely clarify.</p></abstract>ARTICLE2021-04-03T00:00:00.000+00:00Antioxidant and antihyperglycemic activities of radical leaves in streptozocin-induced diabetic ratshttps://sciendo.com/article/10.2478/acph-2021-0045<abstract><title style='display:none'>Abstract</title><p><italic>Scorzonera</italic> species are used for treating various diseases. They are consumed raw, especially in the spring, and have nutritious and dietetic values. This study evaluated the antidiabetic and antioxidant effects of ethanolic extracts of <italic>Scorzonera cinerea</italic> (Sc) radical leaves in diabetes mellitus. Five random groups of Wistar rats (<italic>n</italic> = 8) were created – control, diabetic, acarbose, Sc-Dried, and Sc-Frozen. Phenolic profiles of extracts were determined by HPLC. Free radical scavenging capacity was measured using DPPH and ABTS tests. The inhibitory effects of Sc extracts on α-glucosidase and α-amylase activities were also evaluated. Moreover, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities, glutathione (GSH) concentration, malondialdehyde (MDA), total antioxidant status (TAS) and total oxidant status (TOS) were analyzed in the liver tissues. While dried <italic>Scorzonera</italic> extract was more effective in α-amylase inhibitory activity, frozen <italic>Scorzonera</italic> extract was more effective in α-glucosidase inhibitory activity. Sc-Dried and Sc-Frozen extracts lowered blood glucose and HbA<sub>1c</sub> levels, they also increased insulin. Although liver MDA and TOS were significantly increased in the diabetic group, their values were significantly lower in the Sc-Dried- and Sc-Frozen-treated groups. GSH, TAS, and anti-oxidant enzyme activities decreased in the diabetic group, but Sc-Dried and Sc-Frozen supplements significantly enhanced liver antioxidant values. In conclusion, <italic>S</italic>. <italic>cinerea</italic> treatment exerts potential hypoglycemic and antioxidant effects in diabetes. Thus, it can be considered as a candidate dietary supplement for health benefits in diabetes.</p></abstract>ARTICLE2021-04-03T00:00:00.000+00:00Quality-by-design in pharmaceutical development: From current perspectives to practical applicationshttps://sciendo.com/article/10.2478/acph-2021-0039<abstract><title style='display:none'>Abstract</title><p>Current pharmaceutical research directions tend to follow a systematic approach in the field of applied research and development. The concept of quality-by-design (QbD) has been the focus of the current progress of pharmaceutical sciences. It is based on, but not limited, to risk assessment, design of experiments and other computational methods and process analytical technology. These tools offer a well-organized methodology, both to identify and analyse the hazards that should be handled as critical, and are therefore applicable in the control strategy. Once implemented, the QbD approach will augment the comprehension of experts concerning the developed analytical technique or manufacturing process. The main activities are oriented towards the identification of the quality target product profiles, along with the critical quality attributes, the risk management of these and their analysis through <italic>in silico</italic> aided methods. This review aims to offer an overview of the current standpoints and general applications of QbD methods in pharmaceutical development.</p></abstract>ARTICLE2021-04-03T00:00:00.000+00:00Propolis – quality analysis and use in topical formulationshttps://sciendo.com/article/10.2478/acph-2021-0044<abstract><title style='display:none'>Abstract</title><p>The aim of this study was to produce propolis extracts, assess their quality and effect on skin cells and determine the penetration of active ingredients from designed semi-solid topical formulations. The use of higher-concentration ethanol and a larger amount of raw material allows extracting a larger quantity of active ingredients from raw propolis. Ultrasound extraction is an effective method for the production of aqueous extracts of propolis. The results show that depending on concentration, propolis extracts reduce the viability of keratinocytes. The phenolic compounds under observation penetrated the epidermis and dermis from designed formulations. The base of semi-solid formulation influences the efficacy of propolis preparations. The overall quantity of phenolic compounds that penetrated the skin was around 2 % from the ointment and 1.5 % from the cream.</p></abstract>ARTICLE2021-04-03T00:00:00.000+00:00Identification and pharmacokinetics of saponins in after oral administration to rats by HPLC-Q-TOF/MS and HPLC-MS/MShttps://sciendo.com/article/10.2478/acph-2021-0033<abstract><title style='display:none'>Abstract</title><p><italic>Rhizoma Anemarrhenae</italic> is a well-known herbal medicine with saponins as its commonly regarded major bioactive components. It is essential to classify the properties of saponins which are associated with their toxicity and efficacy. In this study, 25 compounds were identified by HPLC-Q-TOF/MS in the extract of <italic>Rhizoma Anemarrhenae</italic> and 8 saponins were detected in rat plasma by HPLC-MS/MS after oral administration of this extract. These were neomangiferin, mangiferin, timosaponin E1, timosaponin E, timosaponin B-II, timosaponin B-III, timosaponin A-III and timosaponin A-I. A sensitive and accurate HPLC-MS/MS method was developed and successfully applied to a pharmacokinetic study of the abovementioned eight saponins after oral administration of the <italic>Rhizoma Anemarrhenae</italic> extract to rats. The method validation, including specificity, linearity, precision, accuracy, recovery, matrix effect and robustness, met the requirements of the intended use. The pharmacokinetic parameter, <italic>T</italic><sub>max</sub> value, ranged from 2 to 8 h for these eight saponins whereas their elimination half-life <italic>(t</italic><sub>1/2</sub>) ranged from 4.06 to 9.77 h, indicating slow excretion. The plasma concentrations of these eight saponins were all very low, indicating a relatively low oral bioavailability. All these results provide support for further clinical studies.</p></abstract>ARTICLE2021-04-03T00:00:00.000+00:00Piperazine sulfonamides as DPP-IV inhibitors: Synthesis, induced-fit docking and biological evaluationhttps://sciendo.com/article/10.2478/acph-2021-0034<abstract><title style='display:none'>Abstract</title><p>Diabetes mellitus is a chronic illness that needs persistent medical attention and continuous patient self-management to avoid acute complications. Dipeptidyl peptidase-IV (DPP-IV) inhibitors minimize glucagon and blood glucose levels by increasing the incretin levels, glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic poly-peptide (GIP), leading to insulin secretion from pancreatic beta cells. In the present study, nine 1,4-bis(phenylsulfonyl) piperazine derivatives <bold>1a</bold>-<bold>i</bold> were synthesized and identified using <sup>1</sup>H NMR, <sup>13</sup>C NMR, MS and IR spectroscopies. These compounds were tested <italic>in vitro</italic> and showed inhibitory activity ranging from 11.2 to 22.6 % at 100 µmol L<sup>–1</sup> concentration. Piperazine sulfonamide derivatives were found to be promising DPP-IV inhibitors, where the presence of electron-withdrawing groups such as Cl (<bold>1a</bold>-<bold>c</bold>) improved the activity of the compounds more than electron-donating groups such as CH<sub>3 (</sub><bold>1d</bold>-<bold>f</bold>) at the same position. Additionally, <italic>meta</italic>-substitution is disfavored (<bold>1b</bold>, <bold>1e</bold>, <bold>1g</bold>). Induced-fit docking studies suggested that the targeted compounds <bold>1a</bold>-<bold>i</bold> occupy the binding domain of DPP-IV and form H-bonding with the backbones of R125, E205, E206, F357, K554, W629, Y631, Y662 and R669.</p></abstract>ARTICLE2021-04-03T00:00:00.000+00:00New derivatives of sulfonylhydrazone as potential antitumor agents: Design, synthesis and cheminformatics evaluationhttps://sciendo.com/article/10.2478/acph-2021-0043<abstract><title style='display:none'>Abstract</title><p>Phosphoinositide 3-kinase α (PI3Kα) is a propitious target for designing anticancer drugs. A series of new <italic>N</italic>’-(diphenylmethylene)benzenesulfonohydrazide was synthesized and characterized using FT-IR, NMR (<sup>1</sup>H and <sup>13</sup>C), HRMS, and elemental analysis. Target compounds exhibited an antiproliferative effect against the human colon carcinoma (HCT-116) cell line. Our cheminformatics analysis indicated that the <italic>para</italic>-tailored derivatives [<italic>p</italic>-NO<sub>2</sub> (<bold>3</bold>) and <italic>p</italic>-CF<sub>3</sub> (<bold>7</bold>)] have better ionization potentials based on calculated Moran autocorrelations and ionization potentials. Subsequent <italic>in vitro</italic> cell proliferation assays validated our cheminformatics results by providing experimental evidence that both derivatives <bold>3</bold> and <bold>7</bold> exhibited improved antiproliferative activities against HCT-116. Hence, our results emphasized the importance of electron-withdrawing groups and hydrogen bond-acceptors in the rational design of small-molecule chemical ligands targeting PI3Kα. These results agreed with the induced-fit docking against PI3Kα, highlighting the role of <italic>p</italic>-substituted aromatic rings in guiding the ligand-PI3Kα complex formation, by targeting a hydrophobic pocket in the ligand-binding site and forming π-stacking interactions with a nearby tryptophan residue.</p></abstract>ARTICLE2021-04-03T00:00:00.000+00:00Pharmacokinetics study of a supersaturatable self-microemulsifying drug delivery system for ellagic acid by UHPLC-Q-TOF-MShttps://sciendo.com/article/10.2478/acph-2021-0031<abstract><title style='display:none'>Abstract</title><p>To evaluate the bioavailability of ellagic acid loaded super-saturatable self-microemulsifying drug delivery system (S-SMEDDS), its pharmacokinetic properties were studied in rats with an ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. The plasma samples were treated by solid-phase extraction method, and gallic acid was used as the internal standard when determining the concentration of ellagic acid. Results showed that the established analytical method was sensitive and accurate, which is applicable to the pharmacokinetic study of ellagic acid. The drug was found to be absorbed rapidly <italic>in vivo</italic>, and the plasma concentration-time curve showed double peaks, indicating that ellagic acid were reabsorbed by entero-hepatic circulation after oral administration. Compared with ellagic acid suspension, the apparent clearance of ellagic acid-loaded S-SMEDDS and SMEDDS reduced significantly, and the <italic>AUC</italic><sub>0~t</sub> of them were 4.7 and 5.8-fold increase, respectively. Therefore, the bioavailability of ellagic acid-loaded S-SMEDDS was higher than that of the suspension and SMEDDS.</p></abstract>ARTICLE2021-04-03T00:00:00.000+00:00en-us-1