Design, Synthesis and Biological Evaluation of Camptothecin Conjugated with NSAIDs as Novel Dual-actin Antitumor Agents

2019 ◽  
Vol 16 (12) ◽  
pp. 1378-1386
Author(s):  
Xingchen Cai ◽  
Weiwei Huang ◽  
Yi Huang ◽  
Lihua Xia ◽  
Miao Liu ◽  
...  
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Human Plasma ◽  
Biological Evaluation ◽  
Effective Control ◽  
Synergistic Activity ◽  
Sd Rats ◽  
Anti Cancer ◽  
Cancer Activity

Objective: The single-agent therapy was unable to provide an effective control of the malignant process, a well-established strategy to improve the efficacy of antitumor therapy is the rational design of drug combinations aimed at achieving synergistic effects. Objective: The objective of this study is generating the new potential anticancer agents with synergistic activity. Owing to the unique mechanism of action of Camptothecin (CPT), it has shown abroad spectrum of anti-cancer activity against human malignancies, and growing evidence revealed that Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) reduce the risk of different kinds of cancers. So four CPT-NSAIDs conjugates were synthesized and evaluated. Methods: In this study, a series of novel CPT - NSAIDs derivatives were synthesized by esterification. These new compounds were evaluated for in vitro antitumor activity against tumor cell lines A549, Hela, HepG2, HCT116 by MTT assay. To probe the required stabilities as prodrugs, stability tests were studied in human plasma. To further evaluate the stability of Ketoprofen-CPT in vivo, the female SD rats were used to determine the pharmacokinetics following a single oral dose. Results: In vitro results showed that Ketoprofen-CPT and Naproxen-CPT conjugates possessed nice efficacy. In a molecular docking model, the two conjugates interacted with Topo I-DNA through hydrogen bonds, <pi>-<pi> stacking and so on.In human plasma results showed that the prodrug was converted to ketoprofen and another compound. The female SD rats were used to determine the pharmacokinetics following a single oral dose, the half-life (t1/2) of Ketoprofen-CPT was approximately 12 h which was much longer than that of CPT. Conclusion: Good activity was noted for some compounds will be helpful for the design of dualaction agents with most promising anti-cancer activity.

scholarly journals Anti-Obesity Activity, Anti-Cancer Activity and Single Oral Dose Toxicity of Inonotus xeranticus Extracts

2007 ◽  
Vol 23 (3) ◽  
pp. 253-261 ◽  
Author(s):  
Eun-Hee Kang ◽  
In-Kyoung Lee ◽  
Mi-Hyun Hwang ◽  
Jae-Young Choi ◽  
Zhi-Qiang Chang ◽  
...  
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Anti Cancer ◽  
Cancer Activity

scholarly journals Convenient Synthesis and Biological Evaluation of Bis(indolyl)methane Alkaloid and Bis(aryl)alkanes Derivatives with Anti-cancer Properties  

2020 ◽  
Author(s):  
Liang Qi ◽  
Linxia Xiao ◽  
Rui Lin
Keyword(s):  
Carcinoma Cell ◽  
A549 Cells ◽  
Biological Evaluation ◽  
Primary Amines ◽  
Convenient Synthesis ◽  
Anti Cancer ◽  
High Yields ◽  
Synthesis And Biological Evaluation ◽  
Cancer Activity

An efficient and metal free methodology for the synthesis of bis(indolyl)methanes (BIMs) and bis(aryl)alkanes derivatives in the presence of B(C6F5)3 by the condensation of primary amines with pyruvates with good to high yields have been successfully developed. Some BIMs derivatives displayed good in vitro antitumor activity, screened by MTT assay. Compound 3b show the best anti-cancer activity against lung carcinoma cell A549 cells with IC50 of 4.52 µM.

Effect of Aspirin on the Thrombelastogram of Human Blood

1973 ◽  
Vol 30 (03) ◽  
pp. 494-498 ◽  
Author(s):  
G de Gaetano ◽  
J Vermylen
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Platelet Function ◽  
Human Blood ◽  
Platelet Rich Plasma ◽  
Plasma Samples ◽  
Release Reaction ◽  
Platelet Release

SummaryThrombelastograms of both native blood and re-calcified platelet-rich plasma samples taken from subjects given a single oral dose of aspirin (1 gram) were not significantly different from the pretreatment recordings. Aspirin also did not modify the thrombelastogram when preincubated in vitro with platelet-rich plasma at concentrations inhibiting the platelet “release reaction” by collagen. Thrombelastography therefore cannot evaluate the effect of aspirin on platelet function.

scholarly journals Synergistic Action of Stilbenes in Muscadine Grape Berry Extract Shows Better Cytotoxic Potential Against Cancer Cells Than Resveratrol Alone

Biomedicines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 96 ◽  
Author(s):  
Subramani Paranthaman Balasubramani ◽  
Mohammad Atikur Rahman ◽  
Sheikh Mehboob Basha
Keyword(s):  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Biological Activities ◽  
Grape Berry ◽  
Similar Response ◽  
Synergistic Activity ◽  
Anti Cancer ◽  
Muscadine Grape ◽  
Berry Extracts ◽  
Cancer Activity

Muscadine grape is rich in stilbenes, which include resveratrol, piceid, viniferin, pterostilbene, etc. Resveratrol has been extensively studied for its biological activities; however, the synergistic effect of stilbene compounds in berry extracts is poorly understood. The aim of this study was to evaluate the anti-cancer activity of stilbene-rich muscadine berry extract and pure resveratrol. Stilbenes were extracted from ripened berries of muscadine grape cultivars, Pineapple, and Southern Home. HPLC analysis was performed to determine quantity of stilbenes. The extracts were tested for their cytotoxic activity against A549 (lung carcinoma cells), triple negative breast cancer (HCC-1806) and HepG2 (human liver cancer) cells. The stilbene-rich extracts of the muscadine berry extracts showed cytotoxic activity against all of the cells tested. The extracts at 1 μg/mL induced death in 50–80% of cells by 72 h of treatment. About 50 μg/mL of resveratrol was required to induce a similar response in the cells. Further, modulation of genes involved in tumor progression and suppression was significantly (p < 0.0005) higher with the HepG2 cells treated with stilbene-rich berry extracts than the pure resveratrol. This shows that the synergistic activity of stilbenes present in muscadine grape berries have more potent anti-cancer activity than the resveratrol alone.

scholarly journals Evaluation of the anti-cancer activity of the triterpenoidal saponin fraction isolated from the traditional Chinese medicine Conyza blinii H. Lév.

RSC Advances ◽  
2017 ◽  
Vol 7 (6) ◽  
pp. 3408-3412 ◽  
Author(s):  
Long Ma ◽  
Haiyan Liu ◽  
Lingpei Meng ◽  
Ping Qin ◽  
Botao Zhang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Anti Cancer ◽  
Saponin Fraction ◽  
Cancer Activity

Triterpenoidal saponins fraction isolated from a traditional Chinese medicine Conyza blinii H. Lév. demonstrates anti-cancer activity both in vitro and in vivo.

Design and synthesis of novel benzimidazoles containing 1,2,3-triazolesas in vitro, anticancer and anti-oxidant agents

2021 ◽  
Vol 25 (11) ◽  
pp. 104-109
Author(s):  
Gullapelli Kumaraswamy ◽  
Ravichandar Maroju ◽  
Srinivas Bandari ◽  
Gouthami Dasari ◽  
Gullapelli Sadanandam
Keyword(s):  
Spectroscopic Methods ◽  
Moderate Activity ◽  
Design And Synthesis ◽  
Anti Cancer ◽  
Excellent Activity ◽  
Test Organisms ◽  
Anti Oxidant ◽  
High Yields ◽  
Cancer Activity

A novel series of 2-(1-((1-substitutedphenyl-1H-1,2,3- triazol-4-yl)methoxy)ethyl)-1-((1-substituted phenyl- 1H-1,2,3-triazol-4-yl)methyl)-1H-benzo[d]imidazole (3a-j)derivatives was synthesized in moderate to high yields. The structures of all the synthesized compounds were characterized by 1HNMR, 13CNMR and Mass spectroscopic methods. The title compounds were screened for their anti-oxidant activity and anti-cancer activity. The cancer activity results reveal that the compounds 3j, 3b and 3f are showing promising activity and remaining compounds exhibited moderate activity against all the tested cancer cell lines. The anti-oxidant activity also shows that the compounds 3c and 3d have shown excellent activity and remaining compounds were also found to exhibit moderate activity against the test organisms employed.

Synthesis, Electronic Structure and Anti-Cancer Activity of the Phenyl Substituted Pyrazolo[1,5-a][1,3,5]triazines

2021 ◽  
Vol 25 ◽  
Author(s):  
Evgenia S. Veligina ◽  
Nataliya V. Obernikhina ◽  
Stepan G. Pilyo ◽  
Oleksiy D. Kachkovsky ◽  
Volodymyr S. Brovarets
Keyword(s):  
Electronic Transition ◽  
Lone Electron Pair ◽  
Electron Pair ◽  
Anti Cancer ◽  
Protein Molecules ◽  
Biological Affinity ◽  
Cancer Types ◽  
Derivatives Of ◽  
Cancer Activity

: Background: Synthesis of a series of 2-(dichloromethyl)pyrazolo[1,5- a][1,3,5]triazines was carried out and evaluated in vitro for their anticancer activity against a panel of 60 cell lines derived from nine cancer types. The joint quantum-chemical and experimental study of the influence of the extended πconjugated phenyl substituents on the electron structure of the pyrazolo[1,5-a][1,3,5]triazines as Pharmacophores were performed. It is shown that the decrease in the barriers to the rotation of phenyl substituents in compounds 1-7 possibly leads to an increase in the anti-cancer activity, which is in agreement with the change in the parameter biological affinity ϕ0. Analysis of the S0 → S1 electronic transitions (π→π*) of the pyrazolo[1,5-a][1,3,5]triazines shows that an increase in their intensity correlates with anti-cancer activity. Thus, the introduction of phenyl substituents increases the likelihood of investigated pyrazolo[1,5-a][1,3,5]triazines interacting with protein molecules (Biomolecule) by the π stacking mechanism. In both methyl and phenyl derivatives of pyrazolo[1,5-a][1,3,5]triazines, the second electronic transition includes the n-MO (the level of the lone electron pair in two-coordinated nitrogen atoms). The highest intensity of the η→π* electronic transition is observed in pyrazolo[1,5-a][1,3,5]triazine with pyridine residue, which does not exhibit anti-cancer activity, but exhibits antiviral activity [13]. It can be assumed that the possibility of the formation of [Pharmacophore-Biomolecule] complex by hydrogen bonding ([H-B]) mechanism with protein molecules increases.

scholarly journals Quantification of Fosfomycin in Combination with Nine Antibiotics in Human Plasma and Cation-Adjusted Mueller-Hinton II Broth via LCMS

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 54
Author(s):  
Kelvin Kau-Kiat Goh ◽  
Wilson Ghim-Hon Toh ◽  
Daryl Kim-Hor Hee ◽  
Edwin Zhi-Wei Ting ◽  
Nathalie Grace Sy Chua ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Human Plasma ◽  
Limit Of Detection ◽  
Synergistic Activity ◽  
Limit Of Quantification ◽  
Mueller Hinton ◽  
Antibiotic Drug ◽  
Dosing Regimens ◽  
Antibiotic Combination

Fosfomycin-based combination therapy has emerged as an attractive option in our armamentarium due to its synergistic activity against carbapenem-resistant Gram-negative bacteria (CRGNB). The ability to simultaneously measure fosfomycin and other antibiotic drug levels will support in vitro and clinical investigations to develop rational antibiotic combination dosing regimens against CRGNB infections. We developed an analytical assay to measure fosfomycin with nine important antibiotics in human plasma and cation-adjusted Mueller–Hinton II broth (CAMHB). We employed a liquid-chromatography tandem mass spectrometry method and validated the method based on accuracy, precision, matrix effect, limit-of-detection, limit-of-quantification, specificity, carryover, and short-term and long-term stability on U.S. Food & Drug Administration (FDA) guidelines. Assay feasibility was assessed in a pilot clinical study in four patients on antibiotic combination therapy. Simultaneous quantification of fosfomycin, levofloxacin, meropenem, doripenem, aztreonam, piperacillin/tazobactam, ceftolozane/tazobactam, ceftazidime/avibactam, cefepime, and tigecycline in plasma and CAMHB were achieved within 4.5 min. Precision, accuracy, specificity, and carryover were within FDA guidelines. Fosfomycin combined with any of the nine antibiotics were stable in plasma and CAMHB up to 4 weeks at −80 °C. The assay identified and quantified the respective antibiotics administered in the four subjects. Our assay can be a valuable tool for in vitro and clinical applications.

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