Synthesis, Characterization, andIn VitroAnticancer Evaluation of Novel 2,5-Disubstituted 1,3,4-Oxadiazole Analogue

In this series, we have synthesised a new 2,5-disubstituted 1,3,4-oxadiazole in search of potential therapeutics for cancer. The anticancer activities were evaluated on a panel of 60 cell lines by the National Cancer Institute according to its own screening protocol. Out of the 24 compounds, 11 were selected and evaluated via single high dose (10−5 M). In the next phase, two compounds have been selected for five-dose assay. The compounds 3-(5-benzyl-1,3,4-oxadiazol-2-yl)quinolin-2(1H)-one18(NSC-776965) and 3-[5-(2-phenoxymethyl-benzoimidazol-1-ylmethyl)-[1,3,4]oxadiazol-2-yl]-2-p-tolyloxy-quinoline27(NSC-776971) showed mean growth percentage of 66.23 and 46.61, respectively, in one-dose assay and their GI50values ranging between 1.41–15.8 μM and 0.40–14.9 μM, respectively, in 5-dose assay.

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Synthesis, Characterisation, andIn VitroAnticancer Activity of Curcumin Analogues Bearing Pyrazole/Pyrimidine Ring Targeting EGFR Tyrosine Kinase

BioMed Research International ◽

10.1155/2013/239354 ◽

2013 ◽

Vol 2013 ◽

pp. 1-14 ◽

Cited By ~ 23

Author(s):

Mohamed Jawed Ahsan ◽

Habibullah Khalilullah ◽

Sabina Yasmin ◽

Surender Singh Jadav ◽

Jeyabalan Govindasamy

Keyword(s):

Anticancer Activity ◽

National Cancer Institute ◽

Active Compound ◽

Pyrimidine Ring ◽

Curcumin Analogues ◽

Anticancer Effects ◽

Screening Protocol ◽

One Dose Assay ◽

Potential Therapeutics

In search of potential therapeutics for cancer, we described herein the synthesis, characterization, andin vitroanticancer activity of a novel series of curcumin analogues. The anticancer effects were evaluated on a panel of 60 cell lines, according to the National Cancer Institute (NCI) screening protocol. There were 10 tested compounds among 14 synthesized compounds, which showed potent anticancer activity in both one-dose and 5-dose assays. The most active compound of the series was 3,5-bis(4-hydroxy-3-methylstyryl)-1H-pyrazole-1-yl(phenyl)methanone (10) which showed mean growth percent of −28.71 in one-dose assay and GI50values between 0.0079 and 1.86 µM in 5-dose assay.

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Syntheses and Cytotoxicity Screening of some Novel 1,2,4-Triazine Derivatives against Liver Carcinoma Cell Lines

Letters in Organic Chemistry ◽

10.2174/1570178617666200224104740 ◽

2020 ◽

Vol 17 ◽

Author(s):

W. Abd El-Fattah

Keyword(s):

Acetic Anhydride ◽

Cell Lines ◽

Carcinoma Cell ◽

Aromatic Aldehydes ◽

Liver Carcinoma ◽

Anticancer Activities ◽

Carcinoma Cell Lines ◽

Elemental Analyses ◽

Triazine Derivatives ◽

C Nmr

: In this work, 1,2,4-triazine derivatives were synthesized and evaluated for anticancer activities. Series of 1,2,4-triazine derivatives (4a, b) were prepared via the reaction of N-benzoyl glycine (1) with aromatic aldehydes in presence of fused sodium acetate and acetic anhydride to give 1,3-oxazolinone derivatives (2a, b), followed by condensation with 1-(ethoxycarbonyl) hydrazine (3) in glacial acetic acid. Compounds (4a, b) then reacted with acetic anhydride, ethyl chloroacetate and 2,4-dinitrophenyl hydrazine yielded the corresponding to N-acetyl derivatives (5a, b), N-(ethoxycarbonyl) methyl derivative (6) and 1,2-disubstituted hydrazine (7), respectively. The structures of the 1,2,4-triazine derivatives were confirmed by IR, 1H, 13C NMR, MS and elemental analyses. Anticancer activity of some 1,2,4-triazine derivatives (4-7) have been investigated. The results revealed that compounds 4a (IC50= 2.7μM), 5a (IC50= 1.5μM), and 5b (IC50= 3.9μM) show promising inhibitory growth efficacy compared to a standard antitumor drug (IC50= 4.6μM). These three compounds can be considered as potential agents against human hepatocellular carcinoma cell lines (HepG-2).

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Anticancer Activity and Topoisomerase II Inhibition of Naphthalimides with ω-Hydroxylalkylamine Side-Chains of Different Lengths

Medicinal Chemistry ◽

10.2174/1573406414666180912105851 ◽

2019 ◽

Vol 15 (5) ◽

pp. 550-560

Author(s):

Mateusz D. Tomczyk ◽

Anna Byczek-Wyrostek ◽

Klaudia Strama ◽

Martyna Wawszków ◽

Przemysław Kasprzycki ◽

...

Keyword(s):

Anticancer Activity ◽

Cancer Cells ◽

Cell Lines ◽

Inhibitory Activity ◽

Topoisomerase Ii ◽

Significant Activity ◽

Anticancer Activities ◽

Human Colon Cancer ◽

Substitution Pattern ◽

Topo Ii

Background: The substituted 1,8-Naphthalimides (1H-benzo[de]isoquinoline-1,3(2H)- diones) are known as DNA intercalators stabilizing DNA-Topoisomerase II complexes. This interaction disrupts the cleavage-relegation equilibrium of Topo II, resulting in formation of broken strands of DNA. Objective: To investigate the influence of type of substituents and substitution positions in 1,8- naphthalimde skeleton on the inhibition of Topoisomerase II activity. Methods: The starting 1,8-naphthalimide were prepared from acenaphthene by introduction of appropriate substituents followed by condensation with ω-hydroxylakylamines of different chain length. The substituents were introduced to 1,8-naphthalimide molecule by nucleophilic substitution of leaving groups like nitro or bromo present in 4 or 4,5- positions using the ω- hydroxylalkylamines. The bioactivity of obtained compounds was examined in model cell lines. Results: Antiproliferative activity of selected compounds against HCT 116 human colon cancer cells, human non-small cell lung cells A549 and non-tumorigenic BEAS-2B human bronchial epithelium cells was examined. Several of investigated compounds exhibit a significant activity (IC50 µM to 7 µM) against model cancer cell lines. It was demonstrated that upon treatment with concentration of 200 µM, all derivatives display Topo II inhibitory activity, which may be compared with activity of Amonafide. Conclusion: The replacement of the nitro groups in the chromophore slightly reduces its anticancer activities, whereas the presence of both nitro group and ω-hydroxylalkylamine chain resulted in seriously increased anticancer activity. Obtained compounds showed Topo II inhibitory activity, moreover, influence of the substitution pattern on the ability to inhibit Topo II activity and cancer cells proliferation was observed.

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Design, Synthesis, In Vitro Anti-cancer Activity, ADMET Profile and Molecular Docking of Novel Triazolo[3,4-a]phthalazine Derivatives Targeting VEGFR-2 Enzyme

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180412123833 ◽

2018 ◽

Vol 18 (8) ◽

pp. 1184-1196 ◽

Cited By ~ 13

Author(s):

Abdel-Ghany A. El-Helby ◽

Helmy Sakr ◽

Rezk R.A. Ayyad ◽

Khaled El-Adl ◽

Mamdouh M. Ali ◽

...

Keyword(s):

Breast Cancer ◽

Molecular Docking ◽

Cell Lines ◽

Colon Adenocarcinoma ◽

Human Colon ◽

Kinase Assay ◽

Anticancer Activities ◽

In Silico Admet ◽

Human Colon Adenocarcinoma ◽

Mcf 7

Background: Extensive studies were reported in the synthesis of several phthalazine derivatives as promising anticancer agents as potent VEGFR-2 inhibitors. Vatalanib (PTK787) was the first anilinophthalazine published derivative as a potent inhibitor of VEGFR. The discovery of vatalanib as a clinical candidate led to the design and synthesis of different anilinophthalazine derivatives as potent inhibitors for VEGFR-2. The objective of present research work is the synthesis of new agents with the same essential pharmacophoric features of the reported and clinically used VEGFR-2 inhibitors (e.g vatalanib and sorafenib). The main core of our molecular design rationale comprised bioisosteric modification strategies of VEGFR-2 inhibitors at four different positions. </P><P> Material and Methods: A correlation between structure and biological activity of our designed phthalazines was established using molecular docking and VEGFR-2 kinase assay. Results and Discussion: In view of their expected anticancer activity, novel triazolo[3,4-a]phthalazine derivatives 5-6a-o and 3-substituted-bis([1,2,4]triazolo)[3,4-a:4',3'-c]phthalazines 9a-b were designed, synthesized and evaluated for their anti-proliferative activity against two human tumor cell lines HCT-116 human colon adenocarcinoma and MCF-7 breast cancer. It was found that, compound 6o the most potent derivative against both HCT116 and MCF-7 cancer cell lines. Compounds 6o, 6m, 6d and 9b showed the highest anticancer activities against HCT116 human colon adenocarcinoma with IC50 of 7±0.06, 13±0.11, 15±0.14 and 23±0.22 µM respectively while compounds 6o, 6d, 6a and 6n showed the highest anticancer activities against MCF-7 breast cancer with IC50 of 16.98±0.15, 18.2±0.17, 57.54±0.53 and 66.45±0.67 µM respectively. Sorafenib as a highly potent VEGFR-2 inhibitor was used as a reference drug with IC50 of 5.47±0.3 and 7.26±0.3 µM respectively. Nine compounds were further evaluated for their VEGFR-2 inhibitory activity. Compounds 6o, 6m, 6d and 9b emerged as the most active counterparts against VEGFR-2 with IC50 values of 0.1±0.01, 0.15±0.02, 0.28±0.03 and 0.38±0.04 µM, respectively comparable to that of sorafenib (IC50 = 0.1±0.02) µM. Furthermore, molecular docking studies were carried out for all synthesized compounds to investigate their binding pattern and predict their binding affinities towards VEGFR-2 active site. In silico ADMET studies were calculated for the tested compounds. Most of our designed compounds exhibited good ADMET profile. Conclusion: The obtained results showed that, the most active compounds could be useful as a template for future design, optimization, adaptation and investigation to produce more potent and selective VEGFR-2 inhibitors with higher anticancer analogs.

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Fucoxanthin Holds Potential to Become a Drug Adjuvant in Breast Cancer Treatment: Evidence from 2D and 3D Cell Cultures

Molecules ◽

10.3390/molecules26144288 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4288

Author(s):

Fernanda Malhão ◽

Ana Catarina Macedo ◽

Carla Costa ◽

Eduardo Rocha ◽

Alice Abreu Ramos

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

3D Models ◽

Anticancer Activities ◽

Cytotoxic Effects ◽

3D Cultures ◽

3D Cell Cultures ◽

Tumoral Cell ◽

Microscopy Techniques ◽

2D And 3D

Fucoxanthin (Fx) is a carotenoid derived from marine organisms that exhibits anticancer activities. However, its role as a potential drug adjuvant in breast cancer (BC) treatment is still poorly explored. Firstly, this study investigated the cytotoxic effects of Fx alone and combined with doxorubicin (Dox) and cisplatin (Cis) on a panel of 2D-cultured BC cell lines (MCF7, SKBR3 and MDA-MB-231) and one non-tumoral cell line (MCF12A). Fucoxanthin induced cytotoxicity against all the cell lines and potentiated Dox cytotoxic effects towards the SKBR3 and MDA-MB-231 cells. The combination triggering the highest cytotoxicity (Fx 10 µM + Dox 1 µM in MDA-MB-231) additionally showed significant induction of cell death and genotoxic effects, relative to control. In sequence, the same combination was tested on 3D cultures using a multi-endpoint approach involving bioactivity assays and microscopy techniques. Similar to 2D cultures, the combination of Fx and Dox showed higher cytotoxic effects on 3D cultures compared to the isolated compounds. Furthermore, this combination increased the number of apoptotic cells, decreased cell proliferation, and caused structural and ultrastructural damages on the 3D models. Overall, our findings suggest Fx has potential to become an adjuvant for Dox chemotherapy regimens in BC treatment.

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Ampelopsin Inhibits Cell Proliferation and Induces Apoptosis in HL60 and K562 Leukemia Cells by Downregulating AKT and NF-κB Signaling Pathways

International Journal of Molecular Sciences ◽

10.3390/ijms22084265 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4265

Author(s):

Jang Mi Han ◽

Hong Lae Kim ◽

Hye Jin Jung

Keyword(s):

Signaling Pathways ◽

Cell Lines ◽

White Blood Cells ◽

Leukemia Cell ◽

Leukemia Cells ◽

Ros Generation ◽

Anticancer Activities ◽

Nuclear Condensation ◽

Leukemia Cell Lines ◽

Antileukemic Effect

Leukemia is a type of blood cancer caused by the rapid proliferation of abnormal white blood cells. Currently, several treatment options, including chemotherapy, radiation therapy, and bone marrow transplantation, are used to treat leukemia, but the morbidity and mortality rates of patients with leukemia are still high. Therefore, there is still a need to develop more selective and less toxic drugs for the effective treatment of leukemia. Ampelopsin, also known as dihydromyricetin, is a plant-derived flavonoid that possesses multiple pharmacological functions, including antibacterial, anti-inflammatory, antioxidative, antiangiogenic, and anticancer activities. However, the anticancer effect and mechanism of action of ampelopsin in leukemia remain unclear. In this study, we evaluated the antileukemic effect of ampelopsin against acute promyelocytic HL60 and chronic myelogenous K562 leukemia cells. Ampelopsin significantly inhibited the proliferation of both leukemia cell lines at concentrations that did not affect normal cell viability. Ampelopsin induced cell cycle arrest at the sub-G1 phase in HL60 cells but the S phase in K562 cells. In addition, ampelopsin regulated the expression of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors differently in each leukemia cell. Ampelopsin also induced apoptosis in both leukemia cell lines through nuclear condensation, loss of mitochondrial membrane potential, increase in reactive oxygen species (ROS) generation, activation of caspase-9, caspase-3, and poly ADP-ribose polymerase (PARP), and regulation of Bcl-2 family members. Furthermore, the antileukemic effect of ampelopsin was associated with the downregulation of AKT and NF-κB signaling pathways. Moreover, ampelopsin suppressed the expression levels of leukemia stemness markers, such as Oct4, Sox2, CD44, and CD133. Taken together, our findings suggest that ampelopsin may be an attractive chemotherapeutic agent against leukemia.

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A single high dose of dexamethasone increases GAP-43 and synaptophysin in the hippocampus of aged rats

Experimental Gerontology ◽

10.1016/j.exger.2017.08.010 ◽

2017 ◽

Vol 98 ◽

pp. 62-69 ◽

Cited By ~ 1

Author(s):

Vesna Tesic ◽

Milka Perovic ◽

Ivan Zaletel ◽

Mirna Jovanovic ◽

Nela Puskas ◽

...

Keyword(s):

High Dose ◽

Aged Rats ◽

Single High Dose

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Effect of single high dose of spinal clonidine under normal and neuropathic conditions

European Journal of Anaesthesiology ◽

10.1097/00003643-200706001-00656 ◽

2007 ◽

Vol 24 (Supplement 39) ◽

pp. 176

Author(s):

M. Docquier ◽

V. Collet ◽

M. De Kock ◽

P. Lavandhomme

Keyword(s):

High Dose ◽

Single High Dose

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Microbiologic and Immunologic Evaluation of a Single High Dose of Azithromycin for Treatment of Experimental Mycoplasma pneumoniae Pneumonia

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.9.3970-3973.2005 ◽

2005 ◽

Vol 49 (9) ◽

pp. 3970-3973 ◽

Cited By ~ 15

Author(s):

Ana María Ríos ◽

Mónica Fonseca-Aten ◽

Asunción Mejías ◽

Susana Chávez-Bueno ◽

Kathy Katz ◽

...

Keyword(s):

Mycoplasma Pneumoniae ◽

High Dose ◽

Single High Dose ◽

Cytokines And Chemokines ◽

Lung Histopathology ◽

Mycoplasma Pneumoniae Pneumonia

ABSTRACT We evaluated the efficacy of azithromycin therapy given as a single high dose or divided over 5 days for the treatment of mild experimental Mycoplasma pneumoniae pneumonia. Although both azithromycin regimens significantly reduced quantitative cultures, lung histopathology, and pulmonary cytokines and chemokines, there were no significant differences between the two regimens.

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Single High-Dose Vitamin D Supplementation as an Approach for Reducing Ultramarathon-Induced Inflammation: A Double-Blind Randomized Controlled Trial

Nutrients ◽

10.3390/nu13041280 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1280

Author(s):

Jan Mieszkowski ◽

Andżelika Borkowska ◽

Błażej Stankiewicz ◽

Andrzej Kochanowicz ◽

Bartłomiej Niespodziński ◽

...

Keyword(s):

Vitamin D ◽

Inflammatory Marker ◽

Controlled Trial ◽

Vitamin D Supplementation ◽

Oncostatin M ◽

Control Group ◽

High Dose ◽

Double Blind ◽

Single High Dose ◽

High Dose Vitamin

Purpose: A growing number of studies indicate the importance of vitamin D supplementation for sports performance. However, the effects of a single high-dose vitamin D supplementation on ultramarathon-induced inflammation have not been investigated. We here analyzed the effect of a single high-dose vitamin D supplementation on the inflammatory marker levels in ultramarathon runners after an ultramarathon run (maximal run 240 km). Methods: In the study, 35 runners (amateurs) were assigned into two groups: single high-dose vitamin D supplementation group, administered vitamin D (150,000 IU) in vegetable oil 24 h before the start of the run (n = 16); and placebo group (n = 19). Blood was collected for analysis 24 h before, immediately after, and 24 h after the run. Results: Serum 25(OH)D levels were significantly increased after the ultramarathon in both groups. The increase was greater in the vitamin D group than in the control group. Based on post-hoc and other analyses, the increase in interleukin 6 and 10, and resistin levels immediately after the run was significantly higher in runners in the control group than that in those in the supplementation group. Leptin, oncostatin M, and metalloproteinase tissue inhibitor levels were significantly decreased in both groups after the run, regardless of the supplementation. Conclusions: Ultramarathon significantly increases the serum 25(OH)D levels. Attenuation of changes in interleukin levels upon vitamin D supplementation confirmed that vitamin D has anti-inflammatory effect on exercise-induced inflammation.

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