scholarly journals Toxicity of Carlina Oxide—A Natural Polyacetylene from the Carlina acaulis Roots—In Vitro and in Vivo Study

Toxins ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 239
Author(s):  
Artur Wnorowski ◽  
Sylwia Wnorowska ◽  
Kamila Wojas-Krawczyk ◽  
Anna Grenda ◽  
Michał Staniak ◽  
...  
Keyword(s):  
Cell Lines ◽  
Skin Diseases ◽  
Melanoma Cells ◽  
In Vitro Cytotoxicity ◽  
Root Extract ◽  
Extracellular Signal ◽  
Living Organisms ◽  
The 19Th Century

There are several reports indicating that the roots of the Carlina acaulis L. used to be commonly applied as a treatment measure in skin diseases and as an antiparasitic agent, starting from antiquity to the 19th century; however, nowadays, it has lost its importance. Currently, numerous studies are being conducted assessing the possibility of reintroducing C. acaulis-derived extracts to phytotherapy. Determining the safety profile of the main constituents of the plant material is crucial for achieving this goal. Here, we aimed to determine the toxicity profile of carlina oxide, one of the most abundant components of the C. acaulis root extract. We obtained the carlina oxide by distillation of C. acaulis roots in the Deryng apparatus. The purity of the standard was evaluated using GC-MS, and the identity was confirmed by IR, Raman, and NMR spectroscopy. In vitro cytotoxicity was assessed using a panel of human cell lines of skin origin, including BJ normal fibroblasts and UACC-903, UACC-647, and C32 melanoma cells. This was accompanied by an in vivo zebrafish acute toxicity test (ZFET). In vitro studies showed a toxic effect of carlina oxide, as demonstrated by an induction of apoptosis and necrosis in both normal and melanoma cells. Decreased expression of AKT kinase and extracellular signal-regulated kinase 1/2 (ERK1/2) was noted in the UACC-647 melanoma cell line. It was also observed that carlina oxide modified the expression of programmed cell death-ligand 1 (PD-L1) in tested cell lines. Carlina oxide exhibited high in vivo toxicity, with LC50 = 10.13 µg/mL upon the 96 h of exposure in the ZFET test. Here, we demonstrate that carlina oxide displays toxic effects to cells in culture and to living organisms. The data indicate that C. acaulis-based extracts considered for therapeutic use should be completely deprived of carlina oxide.

Effect of cabazitaxel on the growth of human castration-refractory prostate cancer cells in vitro compared to docetaxel and on the anti-tumor properties of the angio-inhibitor PEDF in vivo.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 205-205
Author(s):  
Thomas Nelius ◽  
Courtney Jarvis ◽  
Dalia Martinez-Marin ◽  
Stephanie Filleur
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Cell Lines ◽  
In Vitro Cytotoxicity ◽  
In Vivo Studies ◽  
Raw264.7 Macrophages

205 Background: Docetaxel/DTX and cabazitaxel/CBZ have shown promise in the treatment of metastatic Castration-Refractory Prostate Cancer/mCPRC however, comparative studies are missing. Toxicities of these drugs are significant, urging the need to modify taxane regimens. Recently, low-dose metronomic/LDM treatments using conventional chemotherapeutic drugs have shown benefits in CPRC in improving the effect of anti-angiogenic agents. Previously, we have demonstrated that LDM-DTX in combination with PEDF curbs significantly CRPC growth, limits metastases formation and prolongs survival in vivo. In this study, we intended to compare the cytotoxic effect of CBZ and DTX on CRPC cells in vitro and CL1 tumors in vivo. Methods: PC3, DU145 cell lines were from ATCC.CL1 cells were obtained from androgen-deprived LNCaP cells. Cell proliferation was assessed by crystal violet staining and cell cycle analyses. In vitro cytotoxicity assays were performed on CL1 cells/RAW264.7 macrophages co-cultures treated with PEDF and increasing doses of taxanes. For the in vivo studies, CL1 cells were engineered to stably express the DsRed Express protein +/- PEDF. PEDF anti-tumor effects were assessed on s.c. xenografts treated with DTX (5mg/kg ip ev. 4 day) as reference, CBZ (5mg/kg ip ev. 4 days, 1mg/kg for 10 days, 0.5mg/kg q.a.d. and 0.1mg/kg daily) or placebo. Results: CBZ limits cell proliferation with a greater efficacy than DTX in all CRPC cell lines tested. DU145 presented the largest difference. High doses of taxane blocked tumor cells in mitosis, whereas LDM increased the SubG1 population. This effect was significantly higher in DU145 cells treated with CBZ. In vivo, 5mg/kg CBZ delayed tumor growth more efficiently than 5mg/kg DTX. PEDF/5mg/kg CBZ markedly delayed tumor growth compared to all treatments. Finally, engulfment of tumor cells by macrophages was higher in combined treatments suggesting an inflammation-related process. Conclusions: CBZ is more efficient than DTX both in vitro and in vivo.The data also reinforce PEDF as a promising anti-neoplasic agent in combination with LDM taxane chemotherapies.

scholarly journals Assessment of the toxicity and antiproliferative activity of hemocyanins from Helix lucorum, Helix aspersa and Rapana venosa

2021 ◽  
Vol Volume 53 (Special Issue A) ◽  
pp. 15-21
Author(s):  
I. Yankova ◽  
E Ivanova ◽  
K. Todorova ◽  
A. Georgieva ◽  
V. Dilcheva ◽  
...  
Keyword(s):  
Cell Lines ◽  
Antiproliferative Activity ◽  
Helix Aspersa ◽  
In Vitro Cytotoxicity ◽  
Histopathological Analysis ◽  
Rapana Venosa ◽  
Toxicological Assessment ◽  
Helix Lucorum

Hemocyanins (Hcs) are respiratory, oxygen-carrying metalloproteins that are freely dissolved in the hemolymph of many molluscs and arthropods. The interest in hemocyanins has grown significantly since it was found that they can be successfully used in immunotherapy of neoplastic diseases as non-specific or active stimulators of the immune system. The present study aims to assess the cytotoxicity, in vivo toxicity and antiproliferative activity of hemocyanins isolated from marine snail Rapana venosa (RvH), garden snails Helix lucorum (HlH) and Helix aspersa (HaH). For in vitro safety testing, 3T3 Neutral Red Uptake (NRU) test was used. The experiments for antiproliferative activity of the hemocyanins were performed by MTT assay on a panel of cell lines - a model of breast cancer. The in vivo toxicological assessment was performed by regular clinical examinations of hemocyanin-treated laboratory mice and histopathological analysis of hematoxylin/eosin stained preparations of parenchymal organs. The evaluation of the in vitro cytotoxicity showed that the tested hemocyanins does not induce toxic effects in nontumorigenic epithelial cell lines. In contrast, significant reduction of the viability of human breast carcinoma cell lines was found after treatment with high concentrations of hemocyanins. The in vivo experiments showed no signs of organ and systemic toxicity in the hemocyanin-treated animals. The presented data indicate that Hcs show a potential for development of novel anticancer therapeutics due to their beneficial properties, biosafety and lack of toxicity or side effects. Key words: hemocyanins (Hcs); cytotoxicity; antitumor activity; in vivo biosafety testing.

Anti-CD74-doxorubicin immunoconjugate (IMMU-110) is cytotoxic in non-Hodgkin’s lymphoma (NHL) models and overcomes MDR

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7598-7598 ◽  
Author(s):  
R. Blumenthal ◽  
R. Stein ◽  
R. Michell ◽  
D. M. Goldenberg
Keyword(s):  
Cell Lines ◽  
Day Treatment ◽  
Annexin V ◽  
In Vitro Cytotoxicity ◽  
Kaplan Meier ◽  
Free Doxorubicin ◽  
Daudi Cells ◽  
Cell Implantation

7598 Background: The internalizing LL1 anti-CD74 antibody is an optimal agent for delivering drugs, toxins, or radionuclides to CD74+ cancer cells. Here, we investigated the efficacy of IMMU-110 (Immunomedics, Inc.) in common follicular and aggressive types of NHL cells and in two disseminated non-Burkitt NHL models. Methods: CD74, MDR and MRP expression on NHL cell lines was determined by flow cytometry. In vitro cytotoxicity was assessed by cell cycle analysis of propidium iodide (PI)-stained cells and by measuring apoptotic cells using FITC-Annexin V and PI. In vivo therapy of a single 350-μg dose of IMMU-110 was evaluated in disseminated SUDHL4 and FSCCL. Results: Raji and Daudi Burkitt lines express similar amounts of CD74 (>93% positive cells and a MCF=35), yet a 3-day treatment with 0.8 μg/ml of IMMU-110 results is 18.4% of Raji and 67.9% of Daudi cells in Sub-Go. Aside from Daudi cells that respond with cells shifting into Sub-Go, most other NHL cell lines experience a G2/M block (44%-82% of cells) in response to a 3-day exposure to IMMU-110. Both MDR- and MDR+ NHL cells responded to IMMU-110. Kaplan Meier analysis showed a significant increase in survival of both SUDHL4 (MDR-/MRP-)- and FSCCL (MDR+/MRP+)-bearing SCID mice (P < 0.025) with 100% survival of treated mice vs. 38% survival of untreated mice at 70–77 days post cell implantation. Conclusions: IMMU-110 is cytotoxic in non-Burkitt and in Burkitt NHL cell lines. The magnitude of the cytotoxic response is not related to the amount of CD74 expressed on the cell surface. IMMU-110 is therapeutic in drug-sensitive (SUDHL4) and drug-resistant (FSCCL) NHL models, suggesting that antibody targeting can bypass the MDR drug efflux system that prevents free doxorubicin from being therapeutic. [Table: see text] [Table: see text]

Reversion of physiological drug resistance of weakly basic drugs: The discovery of a new mechanism of PEG-PCL nanoparticles

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13528-e13528
Author(s):  
R. Li ◽  
L. Xie ◽  
X. Li ◽  
Q. Liu ◽  
X. Qian ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Lines ◽  
Cellular Uptake ◽  
Antitumor Effect ◽  
In Vitro Cytotoxicity ◽  
Extracellular Ph ◽  
Fluorescent Particle ◽  
Tumor Ph

e13528 Background: A number of studies have reported the superior antitumor effect of nanoparticles loading chemotherapeutics than the free agents, yet the underlying mechanism has not attract enough attention. The extracellular pH of cancer cells is lower than that of the intracellular pH. Due to this pH gradient, weakly basic drug will protonated extracellularly and display decreased intracellular concentration. In this study, we aimed to reveal a new mechanism of PEG-PCL nanoparticles, namely the reversion of physiological drug resistance. Methods: Tetradrine (Tet), an alkaloid isolated from traditional Chinese medicine, was incorporated into the diblock copolymer methoxy poly(ethylene glycol)-polycaprolactone (mPEG-PCL). In vitro cytotoxicity of free Tet and Tet-loaded nanoparticles at pH7.4 and pH6.8 was compared on four different cancer cell lines. Fluorescent particle cellular uptake study was also used. To evaluate the antitumor effect of the nanoparticles in a more complex model rather than monolayer cell culture, we used Histoculture Drug Resistance Assay (HDRA). The in vivo antitumor effect of the nanoparticles was also studied in ICR mice bearing H22 tumor with different in vivo pH values. Results: In vitro cytotoxicity study in four tumor cell lines showed that the cytotoxicity of free Tet decreased significantly (P<0.05) when the extracellular pH decreased from 7.4 to 6.8, while the cytotoxicity of Tet-loaded nanoparticles increased or didn’t change significantly. The possible mechanism may mainly be the endocytosis of nanoparticles, which was proven by fluorescent particle cellular uptake study. HDRA indicated better tissue penetration of nanoparticles over free Tet. As to in vivo study, the mice with in vivo tumor pH 6.8 and treated with Tet-loaded nanoparticles exhibited best tumor inhibit rate and mildest side effect, suggesting that the use of nanoparticles was more preferable than the manipulation of tumor pH by the use of basic water. Conclusions: Our study clearly demonstrated that the mPEG-PCL nanoparticles could overcome the drug resistance caused by low extracellular pH and enhance drug penetration in the tumor tissue, thus increasing the antitumor efficacy of weakly basic agents. No significant financial relationships to disclose.

scholarly journals Quantification of Berberine in Berberis vulgaris L. Root Extract and Its Curative and Prophylactic Role in Cisplatin-Induced In Vivo Toxicity and In Vitro Cytotoxicity

Antioxidants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 185 ◽  
Author(s):  
Sarfraz Ahmad ◽  
Amina Hussain ◽  
Aroosha Hussain ◽  
Iskandar Abdullah ◽  
Muhammad Sajjad Ali ◽  
...  
Keyword(s):  
Hela Cells ◽  
In Vitro Cytotoxicity ◽  
Root Extract ◽  
Protective Agent ◽  
Protective Effects ◽  
Prophylactic Regimen ◽  
In Vivo Toxicity ◽  
Berberis Vulgaris

Cisplatin is amongst the most potent chemotherapeutic drugs with applications in more than 50% of cancer treatments, but dose-dependent side effects limit its usefulness. Berberis vulgaris L. (B. vulgaris) has a proven role in several therapeutic applications in the traditional medicinal system. High-performance liquid chromatography was used to quantify berberine, a potent alkaloid in the methanolic root extract of B. vulgaris (BvRE). Berberine chloride in BvRE was found to be 10.29% w/w. To assess the prophylactic and curative protective effects of BvRE on cisplatin-induced nephrotoxicity, hepatotoxicity, and hyperlipidemia, in vivo toxicity trials were carried out on 25 healthy male albino Wistar rats (130–180 g). Both prophylactic and curative trials included a single dose of cisplatin (4 mg/kg, i.p.) and nine doses of BvRE (500 mg/kg/day, orally). An array of marked toxicity effects appeared in response to cisplatin dosage evident by morphological condition, biochemical analysis of serum (urea, creatinine, total protein, alanine transaminase, aspartate transaminase, total cholesterol, and triglyceride), and organ tissue homogenates (malondialdehyde and catalase). Statistically-significant (p < 0.05) variations were observed in various parameters. Moreover, histological studies of liver and kidney tissues revealed that the protective effect of BvRE effectively minimized and reversed nephrotoxic, hepatotoxic, and hyperlipidemic effects caused by cisplatin in both prophylactic and curative groups with relatively promising ameliorative effects in the prophylactic regimen. The in vitro cell viability effect of cisplatin, BvRE, and their combination was determined on HeLa cells using the tetrazolium (MTT) assay. MTT clearly corroborated that HeLa cells appeared to be less sensitive to cisplatin and berberine individually, while the combination of both at the same concentrations resulted in growth inhibition of HeLa cells in a remarkable synergistic way. The present validated the use of BvRE as a protective agent in combination therapy with cisplatin.

scholarly journals Cell Proliferation Is Strongly Associated with the Treatment Conditions of an ER Stress Inducer New Anti-Melanoma Drug in Melanoma Cell Lines

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 96
Author(s):  
István Szász ◽  
Viktória Koroknai ◽  
Vikas Patel ◽  
Tibor Hajdú ◽  
Tímea Kiss ◽  
...  
Keyword(s):  
Er Stress ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Melanoma Cells ◽  
Culture Conditions ◽  
Driver Mutations ◽  
Published Data ◽  
Starvation Conditions

HA15 is a new anti-melanoma drug that triggers endoplasmic reticulum (ER) stress and causes deleterious effects on melanoma cell viability due to autophagy and apoptosis, regardless of driver mutations or drug resistance. In this study, we investigated the effect of HA15 on the viability/proliferation of BRAFV600E-mutant melanoma cells using different culture conditions. In contrast to the published data, we did not detect significant melanoma cell death under normal culture conditions using HA15 treatment. Indeed, only cells that were cultured under long-term starvation conditions were sensitive to the drug. Quantitative measurements of ER stress and autophagy markers showed that the compound HA15 does not trigger stress alone but synergistically enhances ER stress under starvation conditions. Importantly, we observed that the viability of normal melanocytes decreased significantly with treatment, even at low HA15 concentrations. Finally yet importantly, we were able to generate HA15-resistant cell lines, which failed by Cerezo et al. In summary, HA15 only influences the viability of cells that are starved for several hours before and during treatment. However, this in vitro setting is far from the in vivo conditions. In addition, our data clearly show that melanoma cells can acquire HA15 resistance. Further studies are needed to prove that HA15 is an effective anti-cancer agent.

scholarly journals Effect of SOCS1 silencing on proliferation and apoptosis of melanoma cells: An in vivo and in vitro study

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769431
Author(s):  
Sheng-Jia Yu ◽  
Zi-Wen Long
Keyword(s):  
Messenger Rna ◽  
Small Interfering Rna ◽  
Melanoma Cells ◽  
Janus Kinase ◽  
Extracellular Signal ◽  
Proliferation And Apoptosis ◽  
Protein Expressions ◽  
Interfering Rna

This study aimed to investigate the effect of SOCS1 silencing on the proliferation and apoptosis of melanoma cells by in vivo and in vitro studies. Immunohistochemical staining was used to detect SOCS1 expression in melanoma tissues and pigmented nevi. Quantitative real-time polymerase chain reaction and western blotting were applied to detect the messenger RNA and protein expressions of SOCS1 in primary human melanocytes and malignant melanoma cell lines (A375, SK-MEL-5, M14, and MV3). Melanoma cells were assigned into mock, negative small interfering RNA, and SOCS1-small interfering RNA groups. The proliferation, cell cycle and apoptosis, and messenger RNA expression of SOCS1 in MV3 and A375 cells were detected using MTT assay, flow cytometry, and quantitative real-time polymerase chain reaction, respectively. The expressions of SOCS1 protein, extracellular signal–regulated kinase, and janus kinase signal transduction and activators of transcription signaling pathways–related proteins were detected using western blotting. After the establishment of subcutaneous xenograft tumor models in nude mice, the latent period, size, volume and growth speed of xenograft tumors in the mock, negative small interfering RNA, and SOCS1-small interfering RNA groups were examined and compared. The results indicated that positive expression rate of SOCS1 was higher in malignant melanoma tissues than in pigmented nevi. MV3 cells had the highest messenger RNA and protein expressions of SOCS1, followed by A357 cells. Compared with the mock and negative small interfering RNA groups, SOCS1-small interfering RNA group showed lower cell viability, elevated cell apoptosis, more cells in G0/G1 phase and less cells in S and G2/M phases, and decreased messenger RNA and protein expressions of SOCS1, p-ERK1/2, p-JAK2, p-STAT1, and p-STAT3. Compared with the mock and negative small interfering RNA groups, the SOCS1-small interfering RNA group showed longer latent period of tumor, smaller tumor size and volume, and smoother tumor growth curve. To conclude, SOCS1 silencing can inhibit proliferation and induce apoptosis of MV3 and A357 melanoma cells in vivo and in vitro by inhibiting extracellular signal–regulated kinase and janus kinase signal transduction and activators of transcription signaling pathways.

Study on the biocompatibility of Ga-based and Al-assisted self-driven liquid metal in cell and animal experiments for drug delivery

2021 ◽  
pp. 1-14
Author(s):  
Fangxing Hou ◽  
Jie Zhang ◽  
Xuyang Sun ◽  
Lei Sheng
Keyword(s):  
Liquid Metals ◽  
Animal Experiments ◽  
Preliminary Evidence ◽  
In Vitro Cytotoxicity ◽  
Future Application ◽  
Living Organisms ◽  
Biological Environment ◽  
Soft Machine

BACKGROUND: With inherent flexibility, high electroconductivity, excellent thermal conductivity, easy printability and biosafety, Ga-based functional liquid metals (LMs) have been extensively evaluated for biomedical applications. When implanted in the biological environment, the safety of the LMs is a major concern for future application. METHODS: In this study, we conducted several biocompatibility assessments through immersion experiments, in vitro cytotoxicity experiments and in vivo embedding experiments. RESULTS: The results showed that both the Al-assisted self-driven LM and the LM per se own good biocompatibility and retrievable properties when contacted with living organisms for a relatively long period of time. CONCLUSION: This study provides preliminary evidence about the biocompatibility of the functional LM materials, such as LM-based soft machine, which would promote and inspire other research to address other tough biomedical issues.

Anti-tumor activity of ADH-1 in vitro and in vivo in combination with paclitaxel in ovarian cancer cell lines

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16050-16050
Author(s):  
M. Gupta ◽  
D. Barnes ◽  
J. Losos ◽  
G. Spehar ◽  
M. Bednarcik ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Combination Therapy ◽  
Tumor Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Xenograft Model ◽  
In Vitro Cytotoxicity ◽  
Anti Tumor Activity

16050 Background: ADH-1 is a novel N-cadherin (Ncad) antagonist. Ncad is a protein present on certain tumor cells and established tumor blood vessels. Its expression on tumor cells increases as they become more aggressive, invasive and metastatic, making it an important target for anti-cancer therapy. ADH-1 was well tolerated in phase I studies and demonstrated evidence of anti-tumor activity in 7 patients whose tumors expressed Ncad. Patient enrollment in two phase II single agent trials concluded at the end of 2006. We report on the anti-tumor activity of ADH-1 in combination with paclitaxel in cancer cell lines in vitro and in the A2780 (Ncad positive) ovarian xenograft model in vivo. Methods: In vitro cytotoxicity of SKOV-3 (ovarian) cells exposed to a fixed ratio of ADH-1 and paclitaxel simultaneously was evaluated by the WST-1 cell proliferation assay. In vivo anti-tumor activity of ADH-1, paclitaxel, and the combination was evaluated in the A2780 xenograft model. ADH-1 100 mg/kg was administered bid IP for 21 days and paclitaxel was administered qod IV for 5 days. Results: In vitro cytotoxicity assays evaluated for combination effects using CalcuSyn software indicated a strong synergistic effect of ADH-1 in combination with paclitaxel (CI <1). In vivo paclitaxel treatment produced a median Time to Endpoint (TTE) (tumor volume >2gm or study end at 60 day) of 32.1 days and 73% Tumor Growth Delay (TGD), compared to control (p=0.028). For the paclitaxel group, there was only one Tumor Free Survivor (TFS) and one transient Complete Responder (CR). ADH-1 produced a TTE of 16.1 and a -13% TGD (p>0.05). The combination of ADH-1 and paclitaxel produced a median TTE of 48.6 days, corresponding to 161% TGD (p<0.0016 compared to untreated controls, p<0.003 for vehicle treated, and p<0.005 compared to paclitaxel alone). The combination therapy generated durable CR in 5 animals, 1 transient CR and 2 PR. The combination therapy had similar toxicity to paclitaxel alone. Conclusions: In this ovarian cancer model, the combination of ADH-1 with paclitaxel produced a synergistic anti-tumor effect. Based in part on these encouraging pre-clinical results, a clinical program of ADH-1 in combination with chemotherapeutic agents has been initiated. No significant financial relationships to disclose.

scholarly journals Design, synthesis and cytotoxic evaluation of 2-amino-4- aryl-6-substituted pyridine-3,5-dicarbonitrile derivatives

2021 ◽  
Vol 20 (10) ◽  
pp. 2127-2133
Author(s):  
Amr S. Abu Lila ◽  
Marwa H. Abdallah ◽  
El-Sayed Khafagy ◽  
Tamer M. Shehata ◽  
Mahmoud S. Soliman ◽  
...  
Keyword(s):  
Cell Lines ◽  
Condensation Reaction ◽  
In Vitro Cytotoxicity ◽  
In Vivo Studies ◽  
Primary Amines ◽  
Binding Modes ◽  
One Pot ◽  
Multicomponent Condensation

Purpose: To synthesize novel pyridine derivatives and evaluate their efficiency as potent inhibitors of cyclin dependent kinase 2 (CDK2) enzyme for cancer therapy.Methods: Pyridine scaffold were synthesized using one-pot multicomponent condensation reaction of arylidine with different primary amines. The cytotoxic potential of the new compounds was assessed using various cell lines. Furthermore, molecular docking studies based on the crystal structure of CDK2 was carried out to determine the possible binding modes that influence the anticancer activities.Results: The results indicate that one-pot multicomponent reaction generated a series of functionalized pyridines with good yield. In vitro cytotoxicity study revealed superior cytotoxicity of the designed compounds against prostate and cervical cancer cell lines compared to 5-fluorouracil (standard anticancer compound) with half-maximal inhibitory concentration (IC50) values of 0.1 – 0.85 and 1.2 –74.1 μM, respectively. Finally, molecular modeling simulation of the newly synthesized compounds showed that they fit well and are stabilized into CDK2 active site via hydrogen bonding and hydrophobic interactions.Conclusion: The results indicate that the newly synthesized pyridine can exert potent anticancer activity presumably via inhibition of CDK2. However, this will need to be confirmed in in vivo studies.

Sign in / Sign up

Export Citation Format

Share Document