Hybrid Quinolinyl Phosphonates as Heterocyclic Carboxylate Isosteres: Synthesis and Biological Evaluation against Topoisomerase 1B (TOP1B)

This work describes, for the first time, the synthesis of dialkyl (2-arylquinolin-8-yl)phosphonate derivatives. The preparation was carried out through a direct and simple process as a multicomponent Povarov reaction of aminophenylphosphonates, aldehydes, and styrenes and subsequent oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) or, alternatively, by a cycloaddition reaction between phosphonate aldimines and acetylenes. Based on phosphonate group structural characteristics, considered as phosphorous isosteres of carboxylic heterocycles, they may present interesting biological properties related to cell proliferation. In the current report, a new series of dialkyl (2-arylquinolin-8-yl)phosphonates have been synthesized and their antiproliferative effect evaluated on different human cancer and embryonic cells, as well as on Leishmania infantum parasites, a eukaryotic protist responsible for visceral leishmaniasis. Thereby, the antitumor effect was assessed in human lung adenocarcinoma cells (A549), human ovarian carcinoma cells (SKOV3), and human embryonic kidney cells (HEK293) versus the non-cancerous lung fibroblasts cell line (MRC5). On the other hand, the antileishmanial activity was tested against both stages of L. infantum cell cycle, namely free-living promastigotes and intramacrophage amastigotes, using a primary culture of Balb/c splenocytes to calculate the selectivity index. Besides the antiproliferative and antileishmanial capacities, their behavior as topoisomerase 1B inhibitors has been evaluated as a possible mechanism of action.

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Design, Synthesis and Biological Evaluation of 3-(3,4,5-Trimethoxyphenyl)- 5-(2-(5-arylbenzo[b]thiophen-3-yl)oxazol-5-yl)isoxazole Derivatives as Anticancer Agents

Letters in Organic Chemistry ◽

10.2174/1570178616666191004105445 ◽

2020 ◽

Vol 17 (5) ◽

pp. 345-351

Author(s):

Syndla Premalatha ◽

G. Rambabu ◽

Islavathu Hatti ◽

Dittakavi Ramachandran

Keyword(s):

Breast Cancer ◽

Anticancer Activity ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

Biological Evaluation ◽

Human Cancer Cell ◽

Human Cancer Cell Lines ◽

Isoxazole Derivatives

A new series of 3-(3,4,5-trimethoxyphenyl)-5-(2-(5-arylbenzo[b]thiophen-3-yl)oxa zol-5- yl)isoxazole derivatives were designed and synthesized. All these derivatives were evaluated for their anticancer activity against various human cancer cell lines such as MCF-7 (breast cancer), A549 (lung cancer), DU-145 (prostate cancer) and MDA MB-231 (breast cancer)-four human cancer cell lines by using MTT assay. Here, etoposide was used as a standard reference drug and most of the compounds were exhibited good anticancer activity with respect to cell lines. Among all compounds, five compounds 11b, 11c, 11f, 11i and 11j showed more potent activity than standard drug, in which, compound 11f was the most promising compound.

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Aberrant Bcl-x splicing in cancer: from molecular mechanism to therapeutic modulation

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-02001-w ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Zhihui Dou ◽

Dapeng Zhao ◽

Xiaohua Chen ◽

Caipeng Xu ◽

Xiaodong Jin ◽

...

Keyword(s):

Cancer Cells ◽

Human Cancer ◽

Structural Characteristics ◽

Therapy Resistance ◽

Regulatory Elements ◽

Aberrant Splicing ◽

Clinical Role ◽

Splicing Isoforms ◽

The Impact ◽

Splicing Patterns

AbstractBcl-x pre-mRNA splicing serves as a typical example to study the impact of alternative splicing in the modulation of cell death. Dysregulation of Bcl-x apoptotic isoforms caused by precarious equilibrium splicing is implicated in genesis and development of multiple human diseases, especially cancers. Exploring the mechanism of Bcl-x splicing and regulation has provided insight into the development of drugs that could contribute to sensitivity of cancer cells to death. On this basis, we review the multiple splicing patterns and structural characteristics of Bcl-x. Additionally, we outline the cis-regulatory elements, trans-acting factors as well as epigenetic modifications involved in the splicing regulation of Bcl-x. Furthermore, this review highlights aberrant splicing of Bcl-x involved in apoptosis evade, autophagy, metastasis, and therapy resistance of various cancer cells. Last, emphasis is given to the clinical role of targeting Bcl-x splicing correction in human cancer based on the splice-switching oligonucleotides, small molecular modulators and BH3 mimetics. Thus, it is highlighting significance of aberrant splicing isoforms of Bcl-x as targets for cancer therapy.

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Comprehensive Evaluation of Biological Effects of Pentathiepins on Various Human Cancer Cell Lines and Insights into Their Mode of Action

International Journal of Molecular Sciences ◽

10.3390/ijms22147631 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7631

Author(s):

Lisa Wolff ◽

Siva Sankar Murthy Bandaru ◽

Elias Eger ◽

Hoai-Nhi Lam ◽

Martin Napierkowski ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Biological Effects ◽

Cancer Cell Lines ◽

Biological Evaluation ◽

Human Cancer Cell ◽

Strand Breaks ◽

Human Cancer Cell Lines

Pentathiepins are polysulfur-containing compounds that exert antiproliferative and cytotoxic activity in cancer cells, induce oxidative stress and apoptosis, and inhibit glutathione peroxidase (GPx1). This renders them promising candidates for anticancer drug development. However, the biological effects and how they intertwine have not yet been systematically assessed in diverse cancer cell lines. In this study, six novel pentathiepins were synthesized to suit particular requirements such as fluorescent properties or improved water solubility. Structural elucidation by X-ray crystallography was successful for three derivatives. All six underwent extensive biological evaluation in 14 human cancer cell lines. These studies included investigating the inhibition of GPx1 and cell proliferation, cytotoxicity, and the induction of ROS and DNA strand breaks. Furthermore, selected hallmarks of apoptosis and the impact on cell cycle progression were studied. All six pentathiepins exerted high cytotoxic and antiproliferative activity, while five also strongly inhibited GPx1. There is a clear connection between the potential to provoke oxidative stress and damage to DNA in the form of single- and double-strand breaks. Additionally, these studies support apoptosis but not ferroptosis as the mechanism of cell death in some of the cell lines. As the various pentathiepins give rise to different biological responses, modulation of the biological effects depends on the distinct chemical structures fused to the sulfur ring. This may allow for an optimization of the anticancer activity of pentathiepins in the future.

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Synthesis, Characterization and Biological Evaluation of Metal Adamantyl 2-Pyridylhydrazone Complexes

Molecules ◽

10.3390/molecules25112530 ◽

2020 ◽

Vol 25 (11) ◽

pp. 2530

Author(s):

Ihsan A. Shehadi ◽

Fatima-Azzahra Delmani ◽

Areej M. Jaber ◽

Hana Hammad ◽

Murad A. AlDamen ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Line ◽

Direct Methods ◽

Cancer Cell Lines ◽

Biological Evaluation ◽

Colorectal Cancer Cell Line ◽

Breast Cancer Cell Lines ◽

Human Cancer Cell Lines

Four new complexes derived from adamantly containing hydrazone (APH) ligand with Cu(II) (1), Co(II) (2), Ni(II) (3) and Zn(II) (4), have been synthesized and characterized using different physicochemical methods. The structure of the ligand APH and its copper complex 1 have been established by single-crystal X-ray diffraction direct methods, which reveal that complex 1 has distorted square-pyramidal geometry. Complexes 1–4 are screened against seven human cancer cell lines namely, breast cancer cell lines (MCF7, T47D, MDA-MB-231), prostate cancer cell lines (PC3, DU145) and the colorectal cancer cell line Coco-2, for their antiproliferative activities. Complex 1 has shown a promising anticancer activity compared to the other ones. The structural and spectroscopic analysis of APH and its complexes are confirmed by DFT calculations.

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Development, Validation and Application of a UHPLC-MS Method for the Quantification of Chios Mastic Gum Triterpenoids in Human Plasma

Planta Medica ◽

10.1055/a-1408-9338 ◽

2021 ◽

Author(s):

Vincent Brieudes ◽

Eleni V. Mikropoulou ◽

Errikos Kallergis ◽

Andriana C. Kaliora ◽

Efstathia Papada ◽

...

Keyword(s):

Human Plasma ◽

Biological Fluids ◽

Structural Characteristics ◽

Biological Properties ◽

Lipid Lowering ◽

High Yield ◽

Limit Of Quantification ◽

Isolation And Characterization ◽

Starting Point ◽

Chios Mastic Gum

AbstractChios mastic gum is the resinous secretion obtained from the barks of the shrub Pistacia lentiscus var. Chia, which is endemic to the Greek island of Chios. Since antiquity, Chios mastic gum has found several uses as a phytotherapeutic remedy, primarily for the treatment of gastrointestinal disorders while recently, Chios mastic gum was also recognized by EMA as an herbal medicinal product with specific indications. Chios mastic gumʼs biological properties are attributed to triterpenes which comprise the major chemical group (approx. 70%) and notably isomasticadienonic acid and masticadienonic acid. However, due to their structural characteristics, the isolation thereof in high yield and purity is challenging and since they are not commercially available, pharmacological studies aiming to assess their biological properties are limited. In the present work, masticʼs phytochemical investigation by UPLC-HRMS is followed by the isolation and characterization of isomasticadienonic acid and masticadienonic acid to be used as analytical standards for their accurate and reliable quantification in human plasma. A UHPLC-tQ-MS method that was developed and validated (in terms of specificity, linearity, limit of quantification, accuracy and precision), for the direct quantification of the targeted compounds in the low ng/mL range of concentration, was subsequently implemented on plasma samples of healthy volunteers thus demonstrating its fitness for purpose. The results presented herein might provide insight to the understanding of this traditional natural product consumed notably for its anti-inflammatory, antioxidant and lipid lowering properties. Moreover, this method might serve as a starting point for any study aiming to monitor bioactive triterpenes in biological fluids.

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Technetium-99m nitrido radiopharmaceuticals with unprecedented biological properties

Brazilian Archives of Biology and Technology ◽

10.1590/s1516-89132002000500019 ◽

2002 ◽

Vol 45 (spe) ◽

pp. 135-142 ◽

Cited By ~ 6

Author(s):

Adriano Duatti ◽

Alessandra Boschi ◽

Licia Uccelli

Keyword(s):

Perfusion Imaging ◽

Short Review ◽

Biological Properties ◽

Biological Evaluation ◽

Chemical Methods ◽

Efficient Tool ◽

Technetium 99M ◽

Heart Perfusion ◽

Diagnostic Agents ◽

Perfusion Tracer

The chemical methods for the production of technetium-99m radiopharmaceuticals containing a terminal Tc<FONT FACE=Symbol>º</FONT>N triple bond have been established more than a decade ago. From that time, the chemistry of nitrido Tc-99m complexes has provided a highly efficient tool for the design and preparation of novel classes of diagnostic agents, and a number of potentially useful radiopharmaceuticals have been discovered. In particular, nitrido technetium-99m tracers have been developed for heart perfusion imaging. In this short review, the chemical and biological properties of the neutral myocardial perfusion tracer bis(N-ethoxy, N-ethyl-dithiocarbamato) nitrido Tc-99m (TcN-NOEt) will be summarized along with the preparation and preliminary biological evaluation of the first class of monocationic nitrido technetium-99m radiopharmaceuticals exhibiting improved biodistribution properties closer to those expected for an ideal perfusion imaging agent.

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Design, synthesis and biological evaluation of imidazopyridine–propenone conjugates as potent tubulin inhibitors

MedChemComm ◽

10.1039/c7md00043j ◽

2017 ◽

Vol 8 (5) ◽

pp. 1000-1006 ◽

Cited By ~ 5

Author(s):

Ibrahim Bin Sayeed ◽

V. Lakshma Nayak ◽

Mohd Adil Shareef ◽

Neeraj Kumar Chouhan ◽

Ahmed Kamal

Keyword(s):

Antitumor Activity ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Biological Evaluation ◽

Human Cancer Cell ◽

Design Synthesis ◽

Human Cancer Cell Lines ◽

Tubulin Inhibitors ◽

Synthesis And Biological Evaluation

A library of imidazopyridine–propenone conjugates (8a–8u) were synthesized and evaluated for their antitumor activity against four human cancer cell lines.

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The Application of Embelin for Cancer Prevention and Therapy

Molecules ◽

10.3390/molecules23030621 ◽

2018 ◽

Vol 23 (3) ◽

pp. 621 ◽

Cited By ~ 12

Author(s):

Jeong-Hyeon Ko ◽

Seok-Geun Lee ◽

Woong Yang ◽

Jae-Young Um ◽

Gautam Sethi ◽

...

Keyword(s):

Cell Death ◽

Cancer Prevention ◽

Cancer Cells ◽

Apoptotic Cell ◽

Human Cancer ◽

Biological Properties ◽

Multiple Cancer ◽

Stat3 Signaling ◽

Oncogenic Pathways ◽

Cell Death Mechanisms

Embelin is a naturally-occurring benzoquinone compound that has been shown to possess many biological properties relevant to human cancer prevention and treatment, and increasing evidence indicates that embelin may modulate various characteristic hallmarks of tumor cells. This review summarizes the information related to the various oncogenic pathways that mediate embelin-induced cell death in multiple cancer cells. The mechanisms of the action of embelin are numerous, and most of them induce apoptotic cell death that may be intrinsic or extrinsic, and modulate the NF-κB, p53, PI3K/AKT, and STAT3 signaling pathways. Embelin also induces autophagy in cancer cells; however, these autophagic cell-death mechanisms of embelin have been less reported than the apoptotic ones. Recently, several autophagy-inducing agents have been used in the treatment of different human cancers, although they require further exploration before being transferred from the bench to the clinic. Therefore, embelin could be used as a potential agent for cancer therapy.

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Gold(I) Complexes with P-Donor Ligands and Their Biological Evaluation

Processes ◽

10.3390/pr9122100 ◽

2021 ◽

Vol 9 (12) ◽

pp. 2100

Author(s):

Monika Richert ◽

Renata Mikstacka ◽

Mariusz Walczyk ◽

Marcin Janusz Cieślak ◽

Julia Kaźmierczak-Barańska ◽

...

Keyword(s):

Cancer Cells ◽

Umbilical Vein ◽

Biological Properties ◽

Biological Evaluation ◽

In Vitro Cytotoxicity ◽

Myelogenous Leukemia ◽

31P Nmr Spectroscopy ◽

Cervix Carcinoma ◽

Ovarian Carcinoma Cell Line

Gold(I) complexes with phosphine ligands—[Au(TrippyPhos)Cl] (1) (TrippyPhos = 1-[2-[bis(tert-butyl)phosphino]phenyl]-3,5-diphenyl-1H-pyrazole), [Au(BippyPhos)Cl]0.5CH2Cl2 (2) (BippyPhos = 5-(di-tert-butylphosphino)-1′, 3′, 5′-triphenyl-1′H-[1,4′]bipyrazole), and [Au(meCgPPh)Cl] (3) (meCgPPh = 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantane—were investigated as types of bioactive gold metallodrugs. Complexes (1)–(3) were characterized using IR, 1H, 13C, 31P NMR spectroscopy, elemental analysis and mass spectrometry (FAB-MS). Complexes of (1) and (2) exhibited substantial in vitro cytotoxicity (IC50 = 0.5–7.0 μM) against both the cisplatin-sensitive and -resistant variants of the A2780 human ovarian carcinoma cell line, as well as against the A549 human lung carcinoma, K562 chronic myelogenous leukemia, and HeLa (human cervix carcinoma) cells. However, among the compounds studied, complex (2) showed the most promising biological properties: the highest stability in biologically relevant media, selectivity towards cancer cells over the non-cancer cells (HUVEC, human umbilical vein endothelial cells), and the highest inhibitory effect on cytosolic NADPH-dependent reductases in A2780 and A2780cis cells among the gold complexes under analysis.

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Whole-Genome Sequencing, Phylogenetic and Genomic Analysis of Lactiplantibacillus pentosus L33, a Potential Probiotic Strain Isolated From Fermented Sausages

Frontiers in Microbiology ◽

10.3389/fmicb.2021.746659 ◽

2021 ◽

Vol 12 ◽

Author(s):

Odysseas Sotirios Stergiou ◽

Konstantinos Tegopoulos ◽

Despoina Eugenia Kiousi ◽

Margaritis Tsifintaris ◽

Aristotelis C. Papageorgiou ◽

...

Keyword(s):

Human Cancer ◽

Draft Genome ◽

Antibiotic Resistance Genes ◽

Probiotic Strain ◽

Biological Properties ◽

Whole Genome ◽

Lactobacillus Pentosus ◽

Fermented Sausages ◽

Probiotic Strains

Lactobacillus is a diverse genus that includes species of industrial and biomedical interest. Lactiplantibacillus pentosus, formerly known as Lactobacillus pentosus, is a recently reclassified species, that contains strains isolated from diverse environmental niches, ranging from fermented products to mammalian gut microbiota. Importantly, several L. pentosus strains present health-promoting properties, such as immunomodulatory and antiproliferative activities, and are regarded as potential probiotic strains. In this study, we present the draft genome sequence of the potential probiotic strain L. pentosus L33, originally isolated from fermented sausages. Comprehensive bioinformatic analysis and whole-genome annotation were performed to highlight the genetic loci involved in host-microbe interactions and the probiotic phenotype. Consequently, we found that this strain codes for bile salt hydrolases, adhesins and moonlighting proteins, and for Class IIb bacteriocin peptides lacking the GxxxG and GxxxG-like motifs, crucial for their inhibitory activity. Its adhesion ability was also validated in vitro, on human cancer cells. Furthermore, L. pentosus L33 contains an exopolysaccharide (EPS) biosynthesis cluster, and it does not carry transferable antibiotic resistance genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and CAZymes analyses showed that L. pentosus L33 possesses biosynthetic pathways for seven amino acids, while it can degrade a wide array of carbohydrates. In parallel, Clusters of Orthologous Groups (COGs) and KEGG profiles of L. pentosus L33 are similar to those of 26 L. pentosus strains, as well as of two well documented L. plantarum probiotic strains. Conclusively, L. pentosus L33 exhibits good probiotic potential, although further studies are needed to elucidate the extent of its biological properties.

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