Newly-Obtained Two Organic-Inorganic Hybrid Compounds Based on Potassium Peroxidomolybdate and Dicarboxypyridinic Acid: Structure Determination, Catalytic Properties, and Cytotoxic Effects of Eight Peroxidomolybdates in Colon and Hepatic Cancer Cells

Two new organic-inorganic hybrid compounds containing dicarboxylic pyridine acids have been obtained and characterized. Both compounds are potassium oxidodiperoxidomolybdates with 2,6-dicarboxylicpyridine acid or 3,5-dicarboxylicpyridine acid moieties, respectively. The chemical formula for the first one is C14H7K3Mo2N2O18 denoted as K26dcpa, the second C7H4K1Mo1N1O11.5—K35dcpa. Their crystal structures were determined using single crystal (K26dcpa) or XRPD—X-ray powder diffraction techniques (K35dcpa). The purity of the compounds was confirmed by elemental analysis. Their thermal stability was determined with the use of non-ambient XRPD. In addition, they were examined by IR spectroscopy methods and catalytic activity studies were performed for them. Catalytic tests in the Baeyer–Villiger reaction and biological activity have been performed for eight compounds: K26dcpa, K35dcpa, and six peroxidomolybdates previously obtained by our group. The anti-proliferative activity of peroxidomolybdenum compounds after 24 h of incubation was studied in vitro against three selected human tumor cell lines (SW620, LoVo, HEP G2) and normal human cells (fibroblasts). The data were expressed as IC50 values. The structure of the investigated oxodiperoxomolybdenum compounds was shown to have influence on the biological activity and catalytic properties. It has been shown that the newly-obtained compound, K35dcpa, is a very efficient catalyst in the Baeyer–Villiger reaction. The best biological activity results were obtained for Na-picO (previously obtained by us), which is a very effective anti-cancer agent towards SW 620 colorectal adenocarcinoma cells.

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Protoflavone-Chalcone Hybrids Exhibit Enhanced Antitumor Action through Modulating Redox Balance, Depolarizing the Mitochondrial Membrane, and Inhibiting ATR-Dependent Signaling

Antioxidants ◽

10.3390/antiox9060519 ◽

2020 ◽

Vol 9 (6) ◽

pp. 519 ◽

Cited By ~ 1

Author(s):

Ahmed Dhahir Latif ◽

Tamás Jernei ◽

Ana Podolski-Renić ◽

Ching-Ying Kuo ◽

Máté Vágvölgyi ◽

...

Keyword(s):

Breast Cancer ◽

Mitochondrial Membrane ◽

Redox Balance ◽

Breast Cancer Cell Lines ◽

Antitumor Action ◽

Hybrid Compounds ◽

Mitochondrial Membrane Depolarization ◽

Ic50 Values ◽

Novel Strategy

Hybrid compounds combine fragments with complementary targets to achieve a common pharmacological goal. This approach represents an increasingly popular strategy for drug discovery. In this work, we aimed to design antitumor hybrid compounds based on an inhibitor of ataxia-telangiectasia and Rad3-related protein (ATR)-dependent signaling, protoapigenone, and a pro-oxidant ferrocene or chalcone fragment. Four new triazole-coupled hybrids were prepared. The compounds were cytotoxic against human breast cancer cell lines in vitro, showing IC50 values in the sub-micromolar range. The nature of interactions between relevant fragments of the hybrids was evaluated by the Chou–Talalay method. Experimental combination treatment with the fragments showed additive effects or slight/moderate synergism, while strong synergism was observed when the fragments were virtually combined into their hybrids, suggesting a relevant pharmacological benefit of the coupling. All hybrids were strong inhibitors of the ATR-mediated activation of Chk1, and they interfered with the redox balance of the cells leading to mitochondrial membrane depolarization. Additionally, they induced late apoptosis and primary necrosis in MDA-MB-231 and MCF-7 breast cancer cells, respectively. Our results demonstrate that coupling the ATR-dependent signaling inhibitor protoflavone with a pro-oxidant chalcone dramatically increases the antitumor activity compared with either fragment alone. Such compounds may offer an attractive novel strategy for the treatment of various cancers.

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Design, Synthesis, and Structural Characterization of Novel Diazaphenothiazines with 1,2,3-Triazole Substituents as Promising Antiproliferative Agents

Molecules ◽

10.3390/molecules24234388 ◽

2019 ◽

Vol 24 (23) ◽

pp. 4388 ◽

Cited By ~ 3

Author(s):

Morak-Młodawska ◽

Pluta ◽

Latocha ◽

Jeleń ◽

Kuśmierz

Keyword(s):

Anticancer Activity ◽

Cell Lines ◽

Human Fibroblasts ◽

Human Tumor ◽

Design Synthesis ◽

Human Tumor Cell Lines ◽

Ic50 Values ◽

Normal Human ◽

Low Cytotoxicity

A series of novel 1,2,3-triazole-diazphenothiazine hybrids was designed, synthesized, and evaluated for anticancer activity against four selected human tumor cell lines (SNB-19, Caco-2, A549, and MDA-MB231). The majority of the synthesized compounds exhibited significant potent activity against the investigated cell lines. Among them, compounds 1d and 4c showed excellent broad spectrum anticancer activity, with IC50 values ranging from 0.25 to 4.66 μM and 0.25 to 6.25 μM, respectively. The most promising compound 1d, possessing low cytotoxicity against normal human fibroblasts NHFF, was used for gene expression analysis using reverse transcription–quantitative real-time PCR (RT–qPCR). The expression of H3, TP53, CDKN1A, BCL-2, and BAX genes revealed that these compounds inhibited the proliferation in all cells (H3) and activated mitochondrial events of apoptosis (BAX/BCL-2).

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Synthesis, Biological Evaluation and Docking Studies of 13-Epimeric 10-fluoro- and 10-Chloroestra-1,4-dien-3-ones as Potential Aromatase Inhibitors

Molecules ◽

10.3390/molecules24091783 ◽

2019 ◽

Vol 24 (9) ◽

pp. 1783 ◽

Cited By ~ 1

Author(s):

Rebeka Jójárt ◽

Péter Traj ◽

Édua Kovács ◽

Ágnes Horváth ◽

Gyula Schneider ◽

...

Keyword(s):

Biological Activity ◽

Inhibitory Action ◽

Molecular Level ◽

Docking Studies ◽

Biological Evaluation ◽

Computational Simulations ◽

Simultaneous Application ◽

Methyl Group ◽

Ic50 Values

Fluorination of 13-epimeric estrones and their 17-deoxy counterparts was performed with Selectfluor as the reagent. In acetonitrile or trifluoroacetic acid (TFA), 10β-fluoroestra-1,4-dien-3-ones were formed exclusively. Mechanistic investigations suggest that fluorinations occurred via SET in acetonitrile, but another mechanism was operative in TFA. Simultaneous application of N-chlorosuccinimide (NCS) and Selectfluor in TFA led to a 1.3:1 mixture of 10β-fluoroestra-1,4-dien-3-one and 10β-chloroestra-1,4-dien-3-one as the main products. The potential inhibitory action of the 10-fluoro- or 10-chloroestra-1,4-dien-3-one products on human aromatase was investigated via in vitro radiosubstrate incubation. The classical estrane conformation with trans ring anellations and a 13β-methyl group seems to be crucial for the inhibition of the enzyme, while test compounds bearing the 13β-methyl group exclusively displayed potent inhibitory action with submicromolar or micromolar IC50 values. Concerning molecular level explanation of biological activity or inactivity, computational simulations were performed. Docking studies reinforced that besides the well-known Met374 H-bond connection, the stereocenter in the 13 position has an important role in the binding affinity. The configuration inversion at C-13 results in weaker binding of 13α-estrone derivatives to the aromatase enzyme.

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Effect of Pregnenolone Derivatives on the Selective Inhibition of 5α-Reductase 2 Activity

Current Enzyme Inhibition ◽

10.2174/1573408015666191105144355 ◽

2020 ◽

Vol 15 (3) ◽

pp. 179-189

Author(s):

Marisa Cabeza ◽

Lucero Bautista ◽

Eugene Bratoeff ◽

Juan Soriano ◽

Yvonne Heuze

Keyword(s):

Biological Activity ◽

Benign Prostatic Hyperplasia ◽

Animal Studies ◽

Reductase Activity ◽

Selective Inhibition ◽

Causative Factor ◽

Prostatic Hyperplasia ◽

Hamster Model ◽

Ic50 Values

Background: Benign prostatic hyperplasia and prostate cancer are androgen-dependent diseases, and dihydrotestosterone (DHT), a 5α-reduced metabolite of testosterone (T), has been implicated as a causative factor in the progression of these diseases. The 5α-reductase enzyme (5α-R) converts T to DHT, which is responsible for increasing cell proliferation, and hence inhibition of this enzyme could lead to potential treatments for these afflictions. Objective: This study focused on evaluating the biological activity of three series of pregnenolone derivatives as inhibitors of 5α-R and as antiandrogens on androgen-dependent glands. Method: To determine the biological activity of these compounds, we evaluated the effect of each one on suppressing the activity of both types of isozymes of 5α-R (1 and 2) by 50% (IC50). Using animal studies, we assessed the effect of these derivatives on the weight of the prostate, seminal vesicles, and diameter of the flank organs of castrated hamsters previously dosed with 1 mg/Kg T. Results: In vitro experiments showed that derivatives 1f, 2b, and 3d were very effective inhibitors of the activity of 5α-R2, showing IC50 values of 21.8, 20, and 15 nM, respectively. Derivatives 2b and 3b showed a lower inhibition effect on 5α-R1. : The data also indicated that derivatives 2b, 1f, 3b, and 3d were very active in reducing prostate weight in the hamster model of benign prostatic hyperplasia. Discussion: Pharmacological experiments showed that pregnenolone derivatives possess an antiandrogenic effect because of the inhibition of DHT production in androgen-dependent glands. Conclusion: The pregnenolone derivatives studied suppressed type 2 5α-reductase activity and because of this, the weight and dimension of androgen-dependent organs were decreased.

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Design of Oleanolic Acid-Based Hybrid Compounds as Potential Pharmaceutical Scaffolds

Letters in Drug Design & Discovery ◽

10.2174/1570180818666210604112451 ◽

2021 ◽

Vol 18 ◽

Author(s):

Vuyolwethu Khwaza ◽

Opeoluwa Oyehan Oyedeji ◽

Blessing Atim Aderibigbe ◽

Eric Morifi ◽

Youmbi Thierry Fonkui ◽

...

Keyword(s):

Oleanolic Acid ◽

Klebsiella Oxytoca ◽

In Vitro Cytotoxicity ◽

Hybrid Compounds ◽

Sulforhodamine B ◽

Cytotoxicity Studies ◽

Sulforhodamine B Assay ◽

Ic50 Values ◽

Further Development

Background: Infectious diseases as well as cancer are the leading causes of death worldwide. Drug resistance usually results in their treatment requiring a combination of two or more drugs. Objective: Oleanolic-based hybrid compounds were prepared via esterification and characterized using FTIR, NMR, and LC-MS. In vitro antibacterial and in vitro cytotoxicity studies were performed. Method: Oleanolic acid was hybridized with selected known pharmaceutical scaffolds via the carboxylic acid functionality to develop therapeutics with increased biological activity. Antibacterial activity was determined using the micro-dilution assay against selected Gram-positive and Gram-negative bacteria and cytotoxicity using the sulforhodamine B assay. Results: Compound 8 displayed potent antibacterial effect against five strains of bacteria such as Bacillus subtilis, Staphylococcus aureus, Proteus vulgaris, Klebsiella oxytoca, and Escherichia coli with MIC values of 1.25, 0.078, 0.078, 1.25, 1.25 mg/mL when compared to the control, oleanolic acid (MIC = 2.5 mg/mL). Furthermore, in vitro cytotoxicity, as determined using the SRB assay, against selected cancer cells revealed that compound 7 was the most cytotoxic to MDA, DU145, and MCF-7 cell lines with IC50 values of 69.87±1.04, 73.2±1.08, and 85.27±1.02 µg/mL, respectively, than oleanolic acid with an IC50 ˃200 µg/mL. Conclusion: Hybridization of oleanolic acids was successful, and further development of these potential antibacterial compounds with reduced cytotoxicity is warranted.

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Synthesis and Cytotoxic Activity Evaluation of New Cu(I) Complexes of Bis(pyrazol-1-yl) Acetate Ligands Functionalized with an NMDA Receptor Antagonist

International Journal of Molecular Sciences ◽

10.3390/ijms21072616 ◽

2020 ◽

Vol 21 (7) ◽

pp. 2616 ◽

Cited By ~ 3

Author(s):

Maura Pellei ◽

Luca Bagnarelli ◽

Lorenzo Luciani ◽

Fabio Del Bello ◽

Gianfabio Giorgioni ◽

...

Keyword(s):

Nmda Receptor ◽

Carboxylic Acid ◽

Receptor Antagonist ◽

Three Dimensional ◽

Human Tumor ◽

Nmda Antagonist ◽

Nmda Receptor Antagonist ◽

Ic50 Values ◽

Drug Resistant Phenotype

In the present article, copper(I) complexes of bis(pyrazol-1-yl) carboxylic acid (LH), bis(3,5-dimethylpyrazol-1-yl) carboxylic acid (L2H), and bis(pyrazol-1-yl) acetates conjugated with an N-methyl-d-aspartate (NMDA) receptor antagonist (LNMDA or L2NMDA) and phosphane ligands (triphenylphosphine or 1,3,5-triaza-7-phosphaadamantane) were synthesized. The selection of an NMDA antagonist for the coupling with LH and L2H was suggested by the observation that NMDA receptors are expressed and play a role in different types of cancer models. All the new complexes showed a significant antitumor activity on a panel of human tumor cell lines of different histology, with cisplatin-sensitive, cisplatin-resistant, or multi-drug-resistant phenotype. Their half maximal inhibitory concentration (IC50) values were in the low- and sub-micromolar range and, in general, significantly lower than that of cisplatin. Interestingly, the fact that all the complexes proved to be significantly more active than cisplatin even in three-dimensional (3D) spheroids of H157 and BxPC3 cancer cells increased the relevance of the in vitro results. Finally, morphological analysis revealed that the most representative complex 8 induced a massive swelling of the endoplasmic reticulum (ER) membrane, which is a clear sign of ER stress.

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Evaluation of Antiproliferative Palladium(II) Complexes of Synthetic Bisdemethoxycurcumin towards In Vitro Cytotoxicity and Molecular Docking on DNA Sequence

Molecules ◽

10.3390/molecules26144369 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4369

Author(s):

Natalia Miklášová ◽

Peter Herich ◽

Juan Carlos Dávila-Becerril ◽

Joaquín Barroso-Flores ◽

Eva Fischer-Fodor ◽

...

Keyword(s):

Biological Activity ◽

Colorectal Carcinoma ◽

Cell Lines ◽

Biological Activities ◽

Human Tumor ◽

Large Family ◽

In Vitro Cytotoxicity ◽

Breast Adenocarcinoma ◽

Human Colorectal Carcinoma

Metallodrugs form a large family of therapeutic agents against cancer, among which is cisplatin, a paradigmatic member. Therapeutic resistance and undesired side effects to Pt(II) related drugs, prompts research on different metal–ligand combinations with potentially enhanced biological activity. We present the synthesis and biological tests of novel palladium(II) complexes containing bisdemethoxycurcumin (BDMC) 1 and 2. Complexes were fully characterized and their structures were determined by X-ray diffraction. Their biological activity was assessed for several selected human tumor cell lines: Jurkat (human leukaemic T-cell lymphoma), HCT-116 (human colorectal carcinoma), HeLa (human cervix epitheloid carcinoma), MCF-7 (human breast adenocarcinoma), MDA-MB-231 (human mammary gland adenocarcinoma), A549 (human alveolar adenocarcinoma), Caco-2 (human colorectal carcinoma), and for non-cancerous 3T3 cells (murine fibroblasts). The cytotoxicity of 1 is comparable to that of cisplatin, and superior to that of 2 in all cell lines. It is a correlation between IC50 values of 1 and 2 in the eight studied cell types, promising a potential use as anti-proliferative drugs. Moreover, for Jurkat cell line, complexes 1 and 2, show an enhanced activity. DFT and docking calculations on the NF-κB protein, Human Serum Albumin (HSA), and DNA were performed for 1 and 2 to correlate with their biological activities.

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FIRST REPORT ON CHEMICAL COMPOSITION AND BIOLOGICAL PROPERTIES OF VOLATILE OIL FROM Psidium firmum O. BERG LEAVES

Química Nova ◽

10.21577/0100-4042.20170710 ◽

2021 ◽

Author(s):

Cassia Fernandes ◽

Pietro Chrystal ◽

Alexandra Pereira ◽

Ana Colli ◽

Livia Stenico ◽

...

Keyword(s):

Chemical Composition ◽

Salmonella Enteritidis ◽

Human Tumor ◽

Volatile Oil ◽

Biological Properties ◽

Dependent Manner ◽

Wide Range ◽

Antiproliferative Agent ◽

Ic50 Values

Brazil has the greatest plant diversity in the world. Many species exhibit a wide range of phytochemical compounds which can be exploited in food, agronomic, pharmacological and medicinal plant industries. Therefore, the chemical composition and in vitro bioactivities of volatile oil from Psidium firmum fresh leaves (PfVO) were investigated for the first time. GC-FID and GC-MS analyses revealed 28 compounds in PfVO. The major ones were α-selinene (20.8%), β-caryophyllene (16.5%) and nerolidol (10.4%). Results showed that PfVO affected the growth of Leishmania amazonensis promastigote forms in a dose-dependent manner; its IC50 value was 14.05 µg/mL. PfVO also exhibited antibacterial activity against Salmonella enteritidis, Yersinia enterocolitica, Staphylococcus aureus, Pseudomonas aeruginosa and Listeria monocytogenes; MIC values ranged from 25 µg/mL to 250 µg/mL. Moreover, PfVO promoted normal cell growth inhibition at 61.02 ± 1.97 µg/mL. Antiproliferative activity was observed against human tumor cell lines; IC50 values of MCF-7 cells, HeLa cells and M059J cells were 47.91 µg/mL, 73.78 µg/mL and 41.94 µg/mL, respectively. Results provided strong evidence of the promising potential of PfVO as a nature-based antileishmanial, antibacterial and antiproliferative agent.

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Bioactivities of essential oils from different parts of Spiranthera odoratissima (Rutaceae)

Rodriguésia ◽

10.1590/2175-7860202071050 ◽

2020 ◽

Vol 71 ◽

Author(s):

Fernando Duarte Cabral ◽

Cassia Cristina Fernandes ◽

Arthur Barcelos Ribeiro ◽

Iara Squarisi Squarisi ◽

Denise Crispim Tavares ◽

...

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Normal Cell ◽

Human Tumor ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines ◽

Ic50 Values ◽

Mcf 7

Abstract This paper aims to investigate, for the first time, in vitro antitubercular, antileishmanial and antiproliferative activities of essential oils (EOs) from S. odoratissima leaves and flowers - grown in midwestern Brazil - against Mycobacterium tuberculosis, promastigote forms of Leishmania amazonensis and human tumor cell lines. Antimycobacterial activity of EOs was evaluated in terms of the minimal inhibitory concentration (MIC). EOs from leaves and flowers showed to be active antimicrobials against M. tuberculosis, since MIC values were 150 µg/mL and 162.5 µg/mL, respectively. Both EOs exhibited significant activity against promastigote forms of L. amazonensis; IC50 values (50% growth inhibition) were 14.36 ± 2.02 (EOs from leaves) and 19.89 ± 2.66 µg/mL (EOs from flowers). Antiproliferative activity in normal (GM07492A, lung fibroblasts) and tumor (MCF-7, HeLa and M059J) cell lines was performed by the XTT assay; results were expressed as IC50 (50% cell growth inhibition) and the selective index was calculated. IC50 values of EOs from leaves and flowers obtained in normal cell lines for were 502.97 ± 40.33 µg/mL and 370.60 ± 2.01 µg/mL, respectively. Antiproliferative activity was observed against human tumor cell lines, whose IC50 values were significantly lower than those obtained in normal cell lines of MCF-7 cells (367.57 ± 4.46 µg/mL-EOs from leaves and 357.70 ± 1.85 µg/mL-EOs from flowers) and M059J cells (492.53 ± 56.67 µg/mL-EOs from leaves and 324.90 ± 6.72 µg/mL-EOs from flowers), thus, indicating selectivity. These in vitro results showed that EOs from S. odoratissima may be an antimycobacterial, antiparasitic and antitumor agent.

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Synthesis and Antitumor Evaluation of Novel N-substituted Norcantharidin Imidazolium Derivatives

Current Organic Synthesis ◽

10.2174/1570179414666170824160901 ◽

2018 ◽

Vol 15 (2) ◽

pp. 237-245 ◽

Cited By ~ 3

Author(s):

Rong-Rong Sun ◽

Jia-Hui Guo ◽

Cui Yang ◽

Li-Juan Yang ◽

Chao Huang

Keyword(s):

Cytotoxic Activity ◽

Cell Lines ◽

Antitumor Agents ◽

Human Tumor ◽

Imidazole Ring ◽

Electronic Effects ◽

Imidazolium Salt ◽

Ic50 Values ◽

Human Lung Carcinoma

Aims and Objectives: Cantharidin is a terpenoid with a high vesicant potency isolated from Mylabris caraganae and various other insects, which originates from the Chinese traditional medicine and has a long history of use as antiproliferative agent. Modified cantharidin derivatives are researched for retainable antitumor activities and lower toxicity. And imidazolium salt is an important building block in drug discovery with pharmacological activities. This study was undertaken to identify that N-substituted norcantharidin imidazolium derivatives possess potential bioactivity. Materials and Method: Using readily available furan, maleic anhydride and imidazoles as starting materials, a series of novel N-substituted norcantharidin imidazolium derivatives have been designed and synthesized. The cytotoxic potential of all newly synthesized N-substituted norcantharidin imidazolium derivatives was assessed in vitro against a panel of human tumor cell lines, Human epidermal carcinoma, human lung carcinoma, liver hepatocellular carcinoma, pheochromocytoma of the rat adrenal medulla. Results: The imidazolium derivatives 6a-6f and 6m-6o, bearing a 5,6-dibromohexahydro-4,7-epoxyisobenzofuran- 1,3-dione or 5-bromo-7-oxabicyclo[2.2.1]hepta- 2,5-diene-2,3-dicarboxylate and electron-donating group, carbonyl and propenyl substituent at position-1 of the imidazole ring, were found to be the most potent compounds as antitumor agents. Notably, compounds 6m and 6n exhibited cytotoxic activity selectively against Hela and A549 cell lines with IC50 values 1.38-fold, 5.04-fold, lower than DDP, while compound 6f showed powerful inhibitory activities selectively against Hela and PC12 cell lines. Conclusion: Steric and electronic effects have an important role in determining the cytotoxic activity of imidazolium salts. The norcantharidin-imidazole 6f, 6m, 6n and 6o can be considered to be promising leads for further structural modifications guided by the valuable information derivable.

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