Palladium Complexes with 3-Substituted Derivatives of 5-Methyl-5-(4-pyridyl)hydantoins. Synthesis, Study and in vitro Cytotoxicity

Six palladium(II) and palladium(IV) complexes with 3-ethyl-5-methyl-5-(4-pyridyl)hydantoin, 3-propyl-5-methyl-5-(4-pyridyl)hydantoin and 3-benzyl-5-methyl-5-(4-pyridyl)hydantoin were synthe-sized. The complexes were identified and characterized by elemental analysis, IR, 1H, 13C NMR spec-tra etc. On the data obtained the molecular formulae of the new palladium complexes were proposed. The cytotoxicity of the complexes was evaluated in vitro using a panel of human tumour cell lines. The re-sults demonstrate that the Pd(II) complex with 3-benzyl-5-methyl-5-(4-pyridyl)hydantoin exerts cyto-toxicity as compared to the other studied Pd(II) complexes in all tested cell lines

New Samarium(III), Gadolinium(III), and Dysprosium(III) Complexes of Coumarin-3-Carboxylic Acid as Antiproliferative Agents

New complexes of samarium(III), gadolinium(III), and dysprosium(III) with coumarin-3-carboxylic acid (HCCA) were prepared by the reaction of the ligand with respective metal nitrates in ethanol. The structures of the final complexes were determined by means of physicochemical data, elemental analysis, IR and Raman spectra. The metal-ligand binding mode in the new Ln(III) complexes of coumarin-3-carboxylic acid was elucidated. The vibrational study gave evidence for bidentate coordination of CCA− to Ln(III) ions through the carbonylic oxygen and the carboxylic oxygen atoms. The complexes were tested for antiproliferative activitiy on the chronic myeloid leukemia-derived K-562, overexpressing the BCR-ABL fusion protein. Cytotoxicity towards tumor cells was determined for a broad concentration range. The samarium salt exerted a very weak antiproliferative effect on these cells. This is in contrast to the lanthanide complexes, especially samarium complex, which exhibited potent antiproliferative activity. The present study confirms our previous observations that the lanthanide complexes of coumarins exhibit antiproliferative activity towards K-562 cell line

Synthesis, Characterization, and Cytotoxic Activity of New Lanthanum(III) Complexes of Bis-Coumarins

Complexes of lanthanum(III) with bis-coumarins: 3,3′-benzylidene-bis(4-hydroxy-2H-1-benzopyran-2-one) (H(2)L1) and bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-(1H-pyrazol-3-yl)-methane (H(2)L2) were synthesized by reaction of lanthanum(III) salt and the ligands, in amounts equal to metal : ligand molar ratio of 1 : 2. The complexes were prepared by adding an aqueous solution of lanthanum(III) salt to an aqueous solution of the ligand subsequently raising the pH of the mixture gradually to circa 5.0 by adding dilute solution of sodium hydroxide. The lanthanum(III) complexes with bis-coumarins were characterized by different physicochemical methods—elemental analysis, IR-, (1)H-, and (13)C-NMR-spectroscopies, and mass spectral data. The spectral data of lanthanum(III) complexes were interpreted on the basis of comparison with the spectra of the free ligands. This analysis showed that in the La(III) complexes, the ligands coordinated to the metal ion through both deprotonated hydroxyl groups. On the basis of the ν(C=O) red shift observed, participation of the carbonyl groups in the coordination with the metal ion was also suggested. In the present study, we performed a cytotoxic-effects screening of the lanthanum complexes with H(2)L1 and H(2)L2 in a panel of human tumor cell lines, using the standard MTT-dye reduction assay for cell viability. The panel consisted of the acute myeloid leukemia-derived HL-60 and the chronic myeloid leukemia-derived BV-173. Following a 24- hour treatment of BV-173 cells with lanthanum complex of H(2)L1 at 100 or 200 μM led to a DNA-laddering. The findings suggest that the observed cytotoxicity of the lanthanum complex of H(2)L1 on BV-173 is at least partly mediated through induction of programmed cell death

Curcumin‘s Therapeutic Potential

Куркумата (Curcuma longa L., сем. Zingiberaceae) е подправка, която е широко използвана в индийската медицина. В спектъра на заболяванията, при които намира приложение, влизат жлъчни и чернодробни заболявания, безапетитие, синузит, ревматизъм, навяхвания и рани. Основното биологично активно вещество в корена от куркума е куркуминът, съпътствано от други близкородствени съединения. За терапевтичния потенциал на куркумина има редица данни от експериментални изследвания, както и клинични данни. Многобройни проучвания показват, че той има значителна противотуморна и в частност противомиеломна активност и откриват перспектива за бъдещото му приложение като лекарствен продукт. Лабилността му при орално приложение, както и потенциалните лекарствени взаимодействия с различни медикаменти, ограничават неговото свободно приложение под формата на капсулни и таблетни форми, но приемът му като подправка е показал само и единствено ползи за употребяващите го.Turmeric (Curcuma longa L., Zingiberaceae) is a spice that is widely used in Indian medicine. The spectrum of diseases in which it is applied includes bile and liver diseases, dizziness, sinusitis, rheumatism, sprains and wounds. The main biologically active substance in the turmeric root is curcumin, accompanied by other closely related compounds. For the therapeutic value of curcumin, there are a number of data from experimental studies as well as clinical data. Numerous studies have shown that it has significant anti-tumor and, in particular, anti-myeloma activity, and have discovered prospects for its future use as a medicinal product. Its lability in oral administration as well as potential drug interactions with various drugs restrict its free use in the form of capsule and tablet formulations, but its administration as a spice has only shown benefits to the patients

Cannabinoids Usage In The Fight Against Oncological Diseases

През последното десетилетие класическата химиотерапия отстъпва място на нови фармакологични подходи, насочени към патологично изменените сигнално-трансдукционни пътища. Канабисът е една от множеството древни билки използвани от американските индианци от хилядолетия насам. В наши дни научните данни за ползотворните му ефекти при широк спектър от заболявания непрекъснато нарастват. Има много експериментални данни, както и експериментални модели и при хора изследващи, повлияваните от биологично активните вещества в него, сигнални каскади.В този обзор са описани редица изследвания и клинични проучвания, които показват значителния напредък постигнат последните години при изпозлването на канабиноидите за борба с онкологичните заболявания. Няколко проучвания in vivo и in vitro доказват добрата поносимост и безопасност на канабидиола при хора и животни. Положителния ефект на субстанцията при различни състояния, възпалителни и онкологични трябва да бъде отчетен, но за да навлезе по-пълно в медицинската практика са необходими още много задълбочени проучвания.Over the last decade, classical chemotherapy has given way to new pharmacological approaches aimed at pathologically altered signal transduction pathways. Cannabis is one of the many ancient herbs used by American Indians for millennia. Nowadays, scientific data on its beneficial effects over a wide range of diseases are constantly increasing. There are many experimental data, as well as experimental models, and in humans studying the signal cascades influenced by the biologically active substances in it.This review describes a number of studies and clinical trials that show the significant advances made in recent years in the use of cannabinoids to combat oncological diseases. In vivo and in vitro studies demonstrate the good tolerability and safety of cannabidiol in humans and animals. The positive effect of the substance in various conditions, inflammatory and oncological, should be taken into account, but more extensive research is needed to gain access to medical practice

Prognostic value of plasmablastic morphology and p21, p53 and Cyclin D1 expression in myeloma cells: retrospective study of 122 patients with first time diagnosed Multiple Myeloma

Print version of the article - 2021, published online - 2022.Multiple myeloma (MM) is the most common bone marrow malignancy which is defined with bone marrow infiltration of more than 10% of terminally differentiated plasma cells sive myeloma cells. The aim of this study was to find correlations between the expression of some immunohistochemical markers (Cyclin D1, p53, p21), plasmablastic differentiation and prognosis of MM. Immunohistochemistry was used to detect expression of cell cycle proteins. Bone marrow trephine biopsies of 122 MM patients were analysed to determine the plasmablastic morphology of myeloma cells and myeloma cells expression of immunohistochemical markers (p21, p53, Cyclin D1). The following clinical data of MM patients were obtained: ß2-microglobulin, albumin, haemoglobin, platelet count, glomerular filtration rate (GFR), creatinine, calcium level, M-gradient and presence of osteolytic lesions. These data were compared with the bone marrow histological findings. Plasmablastic differentiation correlated with decreased level of haemoglobin, albumin and GFR. Cyclin D1 expression correlated with significantly higher serum calcium level, more common osteolytic lesions in bones. Patients with p21 expression in myeloma cells had lower albumin levels, higher M-gradient levels and more advanced stage by Salmon – Durie. These results suggest that there are correlations between plasmablastic differentiation, expression of p53, CyclinD1 and p21 and poor prognosis in cases of MM.publishersversionPeer reviewe

Platinum(IV) Complexes of the 1,3,5-Triamino Analogue of the Biomolecule Cis-Inositol Designed as Innovative Antineoplastic Drug Candidates

Metal complexes occupy a special place in the field of treatment and diagnostics. Their main advantages stem from the possibility of fine-tuning their thermodynamic properties and kinetic behavior in the biological milieu by applying different approaches such as properly constructed inner coordination sphere, appropriate choice of ligands, metal oxidation state, redox potential, etc., which are specific to these compounds. Here we discuss the design and synthesis of two octahedral cationic Pt(IV) complexes of the tridentate ligand all-cis-2,4,6-triaminocyclohexane-1,3,5- triol (taci) with composition, fac-[Pt(taci)I3 ] + , 1 and bis-[Pt(taci)2 ] 4+ , 2 as well as the potential for their application as antineoplastic agents. The complexes have been isolated in a solid state as: fac-[Pt(taci)I3 ]I·3H2O (1A), fac-[Pt(taci)I3 ]I (1B), fac-[Pt(taci)I3 ]I·2DMF (1C), bis-[Pt(taci)2 ](CO3 )2 ·6H2O (2A) by changing the acidity of the reaction systems, the molar ratios of the reagents and the counterions, and by re-crystallization. The ligand taci is coordinated through the NH2 -groups, each molecule occupying three coordination places in the inner coordination sphere of Pt(IV). Monitoring of the hydrolysis processes of 1A and 2A at different acidity showed that while 2A remained stable over the study period, the I−-ions in 1A were successively substituted, with the main product under physiologically mimetic conditions being fac,cis-[Pt(taci)I(OH)2 ] + (h2). The antiproliferative tests involved eight cancer cell models, among which chemosensitive (derived from leukemias and solid tumors) and chemoresistant human Acute myeloid leukemia lines (HL-60/Dox, HL-60/CDDP), as well as the non-malignant kidney’ cells HEK-293T showed that the complexes 1A and 2A are characterized by a fundamentally different profile of chemosensitivity and spectrum of cytotoxic activity compared to cisplatin. The new Pt(IV) complexes were shown to be more effective in selectively inhibiting the proliferation of human malignant cells compared to cisplatin. Remarkable activity was recorded for 1A, which showed an effect (IC50 = 8.9 ± 2.4) at more than 16-fold lower concentration than cisplatin (IC50 = 144.4 ± 9.8) against the resistant cell line HL-60/CDDP. In parallel, 1A exhibited virtually the same cytotoxic effect against the parental HL-60 cells (IC50 = 9.0 ± 1.2), where cisplatin displays comparable chemosensitivity (IC50 = 8.3 ± 0.8). The determined resistance indices (RI~1) show unequivocally that the resistant lines are sensitive to both compounds tested; therefore, they are capable of overcoming the mechanisms of cisplatin resistance. The structural features of these compounds and their promising pharmacological properties justify their inclusion in the group of “non-classical metal-based antitumor compounds” and are a prerequisite for the admission of alternative mechanisms of action

In Vitro Evaluation of a Stable Monomeric Gold(II) Complex with Hematoporphyrin IX: Cytotoxicity against Tumor and Kidney Cells, Cellular Accumulation, and Induction of Apoptosis

The antineoplastic potential of a stable monomeric Au(II) complex with hematoporphyrin IX (Hp), namely [Au(II)Hp−2H.(H2O)2], was investigated in a panel of tumor cell lines. The complex exhibits strong cytotoxicity, whereby the leukaemia- and lymphoma-derived cell lines are more sensitive, with IC50 values comparable to those of the reference anticancer drug cisplatin. In contrast, the solid tumor models are more sensitive to the platinum drug. A comparative assessment of both agents against the human kidney cell line 293T has shown that [Au(II)Hp−2H.(H2O)2] is less cytotoxic. The gold complex induces oligonucleosomal DNA fragmentation in tumour cells following 24-hour treatment and hence its cytotoxic effect is at least partly mediated by induction of apoptotic cell death. A prominent intracellular gold accumulation was detected after treating tumor cells with [Au(II)Hp−2H.(H2O)2] which shows that its putative pharmacological targets are readily accessible after a short incubation period

Arylnaphthalene lignans with a focus Linum species: a review on phytochemical, biotechnological and pharmacological potential

Lignans are a large group of dimeric phenylpropanoids with a long and distinguished history of medicinal use in the ancient cultures of many peoples. The two main groups, -aryltetralin and arylnaphthalene lignans, are leading compounds with important pharmacological properties and a wide range of biological activities. While the first group is well studied mainly for the production of podophyllotoxin, for arylnaphthalene lignans, the data on the availability of a sustainable resource for their production is are still insufficient. The Linum genus, comprising approximately 180 species, is notable for its arylnaphthalene lignans production like justicidin B and isojusticidin B. The pharmacological potential of arylnaphthalene lignans includes cytotoxic, antiviral, anti-inflammatory and antiprotozoal effects. The review highlights the use of biotechnology by in vitro cultures for optimising lignan production. Structural elucidation of novel lignans underscores the ongoing diversity and potential discoveries in this botanical domain, providing an important additional information of arylnaphthalene lignans