ارزیابی کیفیت آزمون های چهار گزینه ای دروس تئوری عمومي گروه اندودانتیکس دانشکده دندانپزشکی قزوین در طی سال های تحصیلی 1388 تا 1396

Svrha je ovoga rada bila ispitati citotoksični, proapoptotski, antimigratorni i pro-antioksidacijski učinak metanolnih, acetonskih i etil-acetatnih ekstrakata dvaju vrsta lišaja, i to: Pseudevernia furfuracea i Platismatia glauca na tumorske stanične linije debelog crijeva (HCT-116 i SW-480). Citotoksični efekti na tumorskim staničnim linijama debelog crijeva uspoređeni su s onima na staničnoj liniji normalnih humanih fibroblasta (MRC-5). Citotoksičnost je ispitana MTT testom, stanična migracija Transwell esejom, dok je apoptoza praćena fluorescentnom metodom pomoću akridin narančastog bojila i etidijevog bromida. Prooksidacijski/antioksidacijski učinak praćen je spektrofotometrijskim mjerenjem koncentracije redoks parametara. Ispitani ekstrakti imali su značajan citotoksični učinak na tumorske stanične linije, bez zapaženog utjecaja na normalnu staničnu liniju. Najjača citotoksičnost postignuta je nakon 72 h obrade staničnih linija ekstraktima vrste P. furfuracea (IC50= (21,2±1.3) µg/mL pri obradi HCT-116 stanica etil-acetatnim ekstraktom i IC50=(51.3±0.8) µg/mL pri obradi stanica SW-480 acetonskim ekstraktom). Ekstrakti P. furfuracea imali su značajan proapoptotski i prooksidacijski učinak, dok je metanolni ekstrakt te vrste imao najjači antimigratorni učinak na ispitane tumorske stanične linije. Svi ispitani ekstrakti vrste P. glauca imali su znatan citotoksični učinak na stanice HCT-116 nakon 72 h tretmana (IC50<40 μg/mL), dok su metanolni i acetonski ekstrakti imali citotoksični učinak na stanice SW-480 nakon 24 h, s izraženom proapoptotskom/nekrotskom aktivnošću. Svi navedeni efekti posljedica su induciranog oksidacijskog stresa u tretiranim stanicama. Može se zaključiti da ekstrakti lišaja bitno mijenjaju vijabilnost i migratorni potencijal ispitanih tumorskih staničnih linija karcinoma debelog crijeva. Dobiveni rezultati pokazuju da su stanice HCT-116 osetljivije na ispitane ekstrakte, pri čemu ekstrakti vrste P. furfuracea pokazuju bolji proapototski i antimigratorni učinak. Ispitane vrste lišaja mogu se smatrati izvorima antikancerogenih aktivnih tvari.The aim of this study is to investigate cytotoxic, proapoptotic, antimigratory and pro-antioxidant effects of methanol, acetone and ethyl acetate extracts of lichens Pseudevernia furfuracea and Platismatia glauca on colorectal cancer (HCT-116 and SW-480) cell lines. We compared the cytotoxic effects on colorectal cancer cells with the effects obtained from normal human fibroblast (MRC-5) cell line. Tetrazolium (MTT) test evaluated the cytotoxic effects, Transwell assay evaluated cell migration, acridine orange/ethidium bromide (AO/EB) fluorescent method followed the apoptosis, while prooxidant/antioxidant effects were determined spectrophotometrically through concentration of redox parameters. The tested extracts showed considerable cytotoxic effect on cancer cells with no observable cytotoxic effect on normal cells. Ethyl acetate and acetone extract of P. furfuracea induced the highest cytotoxicity (IC50=(21.2±1.3) μg/mL on HCT-116, and IC50=(51.3±0.8) μg/mL on SW-480 cells, respectively, after 72 h), with noteworthy apoptotic and prooxidant effects, and antimigratory potential of methanol extract. P. glauca extracts induced cytotoxic effects on HCT-116 cells after 72 h (IC50<40 μg/mL), while only methanol and acetone extracts had cytotoxic effects on SW-480 cells after 24 h, with proapoptotic/necrotic activity, as a consequence of induced oxidative stress. In conclusion, lichen extracts changed to a great extent cell viability and migratory potential of colorectal cancer cell lines. HCT-116 cells were more sensitive to treatments, P. furfuracea had better proapoptotic and antimigratory effects, and both investigated lichen species might be a source of substances with anticancer activity

Synthesis, characterization and cytotoxicity of a palladium(II) complex of 3-[(2-hydroxybenzylidene)amino]-2-thioxoimidazolidin-4-one

The polydentate ligand 3-[(2-hydroxybenzylidene)amino]-2-thioxoimidazolidin-4-one was synthesized in the intermolecular cyclocondensation reaction of 2-hydroxybenzaldehyde thiosemicarbazone and ethyl chloroacetate. A novel palladium(II) complex was obtained from cis-[Pd(DMSO)(2)Cl-2] by nucleophilic substitution of both DMSO ligands with the iminic nitrogen and the thiolactamic sulfur from the ligand. The structures of the compounds were characterized based on their spectral data. The cytotoxic activities of the ligand and the palladium(II) complex were studied on the tumor cell lines: human colon carcinoma HCT-116 and SW-480 cells using the MTT viability test. The results showed that the investigated palladium(II) complex had a significantly greater cytotoxic effect compared to that of the ligand

Synthesis, structural characterization, biological activity and molecular docking study of 4,7-dihydroxycoumarin modified by aminophenol derivatives

In the present manuscript, three different 4,7-dihydroxycoumarin derivatives were prepared and structurally characterized by crystallographic and spectroscopic techniques in combination with the B3LYP-D3BJ theoretical method. Cytotoxic and antimicrobial activities of investigated compounds were screened against different cell lines and microorganisms. HCT-116 cells were most sensitive to the 3-(1-(2-hydroxyphenyl)amino) ethylidene)-2,4-dioxochroman-7-yl acetate derivative, while the best antimicrobial activity against Bacillus subtilis ATCC 6633 was shown by 3-(1-(2- hydroxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate. The molecular docking study for all compounds with important epidermal growth factor receptors (EGFR) was performed. The results indicate that the largest contribution to the binding energy is through conventional hydrogen bonds

Synthesis of new Pt(II) complex bearing organoselenium ligands and evaluation of cytotoxic activity of some structurally related Pd(II) complexes

© 2020, Macedonian Journal of Chemistry and Chemical Engineering. Herein we report the synthesis of a new trans-bis(2-phenylselenylmethyl)oxolane)dichloroplati-num(II) complex (Pt1). This newly synthesized complex, together with two structurally related trans-Pd(II) complexes, (trans-bis(2-(phenylselenylmethyl)oxolane) dichloropalladium(II) (Pd1) and trans-bis(2-(phenylselenylmethyl)oxane)dichloropalladium(II) (Pd2), were screened for cytotoxic activity through in vitro studies on the HCT-116 colorectal carcinoma cell line and MRC-5 healthy lung pleura cell line. The activity of the complexes was assessed by comparing it to cisplatin. The cells' viability and proliferation were determined using an MTT (Microculture Tetrazolium Test) assay

Bis(triazinyl)pyridine complexes of Pt(II) and Pd(II): studies of the nucleophilic substitution reactions, DNA/HSA interactions, molecular docking and biological activity

Four new complexes of Pt(II) and Pd(II), [Pd(L1)Cl]Cl 1, [Pd(L2)Cl]Cl 2, [Pt(L1)Cl]Cl 3 and [Pt(L2)Cl]Cl 4 (where L1 = 2,6-bis(5,6-diphenyl-1,2,4-triazin-3-yl)pyridine and L2 = 2,6-bis(5,6-dipropyl-1,2,4-triazin-3-yl)pyridine), were synthesized. Characterization of the complexes was performed using elemental analysis, IR, 1H NMR spectroscopy and MALDI-TOF mass spectrometry. The substitution reactions of 1-4 complexes with L-methionine (L-met), L-cysteine (L-cys) and guanosine-5'-monophosphate (5'-GMP), were studied spectrophotometrically at physiological conditions. Complexes with ligand L1 (1 or 3) were more reactive than those with ligand L2 (2 or 4) by a factor ranging up to 1.57 and 3.71, respectively. The order of reactivity of the nucleophiles was: L-met > L-cys > 5'-GMP. The interactions of complexes with calf thymus-DNA (CT-DNA) and human serum albumin (HSA) were studied by Uv-Vis absorption and fluorescence emission spectroscopy. Competitive binding studies with intercalative agent ethidium bromide (EB) and minor groove binder Hoechst 33258 were performed as well. All studied complexes can interact with DNA through the intercalation and minor groove binding, where the latter was preferred. The binding constants (103 and 104 M-1) for the interaction of complexes with HSA indicate the moderate binding affinity of complexes 1-4 to protein. The trends in the experimental results of binding studies between complexes 3 and 4 with DNA and HSA were compared to those obtained from the molecular docking study. Biological evaluation of cytotoxicity of 1 and 2 on HCT-116 and MDA-MB-231 cell lines showed significant cytotoxic and prooxidative character, while 2 also exerted extraordinary selectivity towards colon cancer in comparison to breast cancer cells. The nucleophilic substitution reactions, DNA/HSA interactions, molecular docking and biological activity of bis(triazinyl)pyridine complexes of Pt(II) and Pd(II) were studied

Synthesis, Crystallographic, Quantum Chemical, Antitumor, and Molecular Docking/Dynamic Studies of 4-Hydroxycoumarin-Neurotransmitter Derivatives

In this contribution, four new compounds synthesized from 4-hydroxycoumarin and tyramine/octopamine/norepinephrine/3-methoxytyramine are characterized spectroscopically (IR and NMR), chromatographically (UHPLC-DAD), and structurally at the B3LYP/6-311++G*(d,p) level of theory. The crystal structure of the 4-hydroxycoumarin-octopamine derivative was solved and used as a starting geometry for structural optimization. Along with the previously obtained 4-hydroxycoumarin-dopamine derivative, the intramolecular interactions governing the stability of these compounds were quantified by NBO and QTAIM analyses. Condensed Fukui functions and the HOMO-LUMO gap were calculated and correlated with the number and position of OH groups in the structures. In vitro cytotoxicity experiments were performed to elucidate the possible antitumor activity of the tested substances. For this purpose, four cell lines were selected, namely human colon cancer (HCT-116), human adenocarcinoma (HeLa), human breast cancer (MDA-MB-231), and healthy human lung fibroblast (MRC-5) lines. A significant selectivity towards colorectal carcinoma cells was observed. Molecular docking and molecular dynamics studies with carbonic anhydrase, a prognostic factor in several cancers, complemented the experimental results. The calculated MD binding energies coincided well with the experimental activity, and indicated 4-hydroxycoumarin-dopamine and 4-hydroxycoumarin-3-methoxytyramine as the most active compounds. The ecotoxicology assessment proved that the obtained compounds have a low impact on the daphnia, fish, and green algae population

AI-Driven Optimization of PCL/PEG Electrospun Scaffolds for Enhanced In Vivo Wound Healing

Here, an artificial intelligence (AI)-based approach was employed to optimize the production of electrospun scaffolds for in vivo wound healing applications. By combining polycaprolactone (PCL) and poly(ethylene glycol) (PEG) in various concentration ratios, dissolved in chloroform (CHCl3) and dimethylformamide (DMF), 125 different polymer combinations were created. From these polymer combinations, electrospun nanofiber meshes were produced and characterized structurally and mechanically via microscopic techniques, including chemical composition and fiber diameter determination. Subsequently, these data were used to train a neural network, creating an AI model to predict the optimal scaffold production solution. Guided by the predictions and experimental outcomes of the AI model, the most promising scaffold for further in vitro analyses was identified. Moreover, we enriched this selected polymer combination by incorporating antibiotics, aiming to develop electrospun nanofiber scaffolds tailored for in vivo wound healing applications. Our study underscores three noteworthy conclusions: (i) the application of AI is pivotal in the fields of material and biomedical sciences, (ii) our methodology provides an effective blueprint for the initial screening of biomedical materials, and (iii) electrospun PCL/PEG antibiotic-bearing scaffolds exhibit outstanding results in promoting neoangiogenesis and facilitating in vivo wound treatment