scholarly journals Synthesis of a Novel Pyrano[2,3-C]pyrazole Enabling PKBβ/AKT2 Inhibitory and in Vitro Anti-Glioma Activity

2021 ◽  
Author(s):  
Ruturajsinh M. Vala ◽  
Vasudha Tandon ◽  
Lynden G Nicely ◽  
Luxia Guo ◽  
Yanlong Gu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Patient Survival ◽  
Pyrazole Derivative ◽  
Inhibitory Function ◽  
Oncogenic Pathways ◽  
Growth Inhibitory ◽  
Anti Cancer ◽  
Glioma Growth ◽  
First Time

<p>A series of novel pyrano[2,3-c]pyrazoles were synthesized and screened for their potential to inhibit kinases and exhibit anti-cancer activity against primary patient derived glioblastoma 2D cells and 3D neurospheres. A collection of 10 compounds were evaluated against glioma cell lines, with compound 4j exhibiting promising glioma growth inhibitory properties. Compound 4j was screened against 139 purified kinases and exhibited low micromolar activity against kinase AKT2/PKBβ. AKT signalling is one of the main oncogenic pathways in glioma and is often targeted for novel therapeutics. Indeed AKT2 levels correlated with glioma malignancy and poorer patient survival. Compound 4j inhibited the 3D neurosphere formation in primary patient derived glioma stem cells and exhibited potent EC<sub>50</sub> against glioblastoma cell lines. Herein we establish a novel biochemical kinase inhibitory function for a pyrano[2,3-c]pyrazole derivative and further report its anti-glioma activity <i>in vitro</i> for the first time.</p>

scholarly journals Synthesis of a Novel Pyrano[2,3-C]pyrazole Enabling PKBβ/AKT2 Inhibitory and in Vitro Anti-Glioma Activity

2021 ◽  
Author(s):  
Ruturajsinh M. Vala ◽  
Vasudha Tandon ◽  
Lynden G Nicely ◽  
Luxia Guo ◽  
Yanlong Gu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Patient Survival ◽  
Pyrazole Derivative ◽  
Inhibitory Function ◽  
Oncogenic Pathways ◽  
Growth Inhibitory ◽  
Anti Cancer ◽  
Glioma Growth ◽  
First Time

<p>A series of novel pyrano[2,3-c]pyrazoles were synthesized and screened for their potential to inhibit kinases and exhibit anti-cancer activity against primary patient derived glioblastoma 2D cells and 3D neurospheres. A collection of 10 compounds were evaluated against glioma cell lines, with compound 4j exhibiting promising glioma growth inhibitory properties. Compound 4j was screened against 139 purified kinases and exhibited low micromolar activity against kinase AKT2/PKBβ. AKT signalling is one of the main oncogenic pathways in glioma and is often targeted for novel therapeutics. Indeed AKT2 levels correlated with glioma malignancy and poorer patient survival. Compound 4j inhibited the 3D neurosphere formation in primary patient derived glioma stem cells and exhibited potent EC<sub>50</sub> against glioblastoma cell lines. Herein we establish a novel biochemical kinase inhibitory function for a pyrano[2,3-c]pyrazole derivative and further report its anti-glioma activity <i>in vitro</i> for the first time.</p>

scholarly journals Design, Synthesis, and Cell Lines Studies of Oleanolic Acid—Hydrogen Sulfide Donor Hybrids

2021 ◽  
Vol 11 (8) ◽  
pp. 3364
Author(s):  
Fenqin Zhao ◽  
Jinyu Li ◽  
Kexin Yue ◽  
Beibei Song ◽  
Erying Sun ◽  
...  
Keyword(s):  
Cell Lines ◽  
Oleanolic Acid ◽  
Cancer Cell ◽  
A549 Cells ◽  
Cancer Cell Lines ◽  
Design Synthesis ◽  
Anti Cancer ◽  
First Time ◽  
Donor Moiety

In order to develop new oleanolic acid (OA) derivatives endowed with improved antitumor activities, for the first time, a number of new hybrid compounds were reported by combining OA or 3-oxooleanolic acid with appropriate H2S-donor moiety, coupled via a suitable linker. The anti-tumor evaluation indicated that they exhibited excellent anti-cancer activities against the tested cancer cell lines. Moreover, 18d with 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione moiety as H2S donor and β-alanine as the linker, showed more potent cytotoxicity against the tested cancer cell lines than OA and 3-oxooleanolic acid, especially for A549 cells. Furthermore, the preferred compound, 18d, preferentially accumulates in cancer cells (13.6 μM) over the matched normal cells LO2 (>100 μM) in vitro. The improved antitumor activity of this hybrid was probably due to its H2S-releasing capability.

scholarly journals Delivery of melittin-loaded niosomes for breast cancer treatment: an in vitro and in vivo evaluation of anti-cancer effect

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Farnaz Dabbagh Moghaddam ◽  
Iman Akbarzadeh ◽  
Ehsan Marzbankia ◽  
Mahsa Farid ◽  
Leila khaledi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Cell Lines ◽  
Encapsulation Efficiency ◽  
Inbred Mice ◽  
Breast Cancer Treatment ◽  
Anticancer Effect ◽  
Anti Cancer

Abstract Background Melittin, a peptide component of honey bee venom, is an appealing candidate for cancer therapy. In the current study, melittin, melittin-loaded niosome, and empty niosome had been optimized and the anticancer effect assessed in vitro on 4T1 and SKBR3 breast cell lines and in vivo on BALB/C inbred mice. "Thin-layer hydration method" was used for preparing the niosomes; different niosomal formulations of melittin were prepared and characterized in terms of morphology, size, polydispersity index, encapsulation efficiency, release kinetics, and stability. A niosome was formulated and loaded with melittin as a promising drug carrier system for chemotherapy of the breast cancer cells. Hemolysis, apoptosis, cell cytotoxicity, invasion and migration of selected concentrations of melittin, and melittin-loaded niosome were evaluated on 4T1 and SKBR3 cells using hemolytic activity assay, flow cytometry, MTT assay, soft agar colony assay, and wound healing assay. Real-time PCR was used to determine the gene expression. 40 BALB/c inbred mice were used; then, the histopathology, P53 immunohistochemical assay and estimate of renal and liver enzyme activity for all groups had been done. Results This study showed melittin-loaded niosome is an excellent substitute in breast cancer treatment due to enhanced targeting, encapsulation efficiency, PDI, and release rate and shows a high anticancer effect on cell lines. The melittin-loaded niosome affects the genes expression by studied cells were higher than other samples; down-regulates the expression of Bcl2, MMP2, and MMP9 genes while they up-regulate the expression of Bax, Caspase3 and Caspase9 genes. They have also enhanced the apoptosis rate and inhibited cell migration, invasion in both cell lines compared to the melittin samples. Results of histopathology showed reduce mitosis index, invasion and pleomorphism in melittin-loaded niosome. Renal and hepatic biomarker activity did not significantly differ in melittin-loaded niosome and melittin compared to healthy control. In immunohistochemistry, P53 expression did not show a significant change in all groups. Conclusions Our study successfully declares that melittin-loaded niosome had more anti-cancer effects than free melittin. This project has demonstrated that niosomes are suitable vesicle carriers for melittin, compare to the free form.

scholarly journals Pharmacoinformatics and Preclinical Studies of NSC765690 and NSC765599, Potential STAT3/CDK2/4/6 Inhibitors with Antitumor Activities against NCI60 Human Tumor Cell Lines

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 92
Author(s):  
Bashir Lawal ◽  
Yen-Lin Liu ◽  
Ntlotlang Mokgautsi ◽  
Harshita Khedkar ◽  
Maryam Rachmawati Sumitra ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Tumor ◽  
Cancer Cell Lines ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Anti Cancer

Signal transducer and activator of transcription 3 (STAT3) is a transcriptional regulator of a number of biological processes including cell differentiation, proliferation, survival, and angiogenesis, while cyclin-dependent kinases (CDKs) are a critical regulator of cell cycle progression. These proteins appear to play central roles in angiogenesis and cell survival and are widely implicated in tumor progression. In this study, we used the well-characterized US National Cancer Institute 60 (NCI60) human tumor cell lines to screen the in vitro anti-cancer activities of our novel small molecule derivatives (NSC765690 and NSC765599) of salicylanilide. Furthermore, we used the DTP-COMPARE algorithm and in silico drug target prediction to identify the potential molecular targets, and finally, we used molecular docking to assess the interaction between the compounds and prominent potential targets. We found that NSC765690 and NSC765599 exhibited an anti-proliferative effect against the 60 panels of NCI human cancer cell lines, and dose-dependent cytotoxic preference for NSCLC, melanoma, renal, and breast cancer cell lines. Protein–ligand interactions studies revealed that NSC765690 and NSC765599 were favored ligands for STAT3/CDK2/4/6. Moreover, cyclization of the salicylanilide core scaffold of NSC765690 mediated its higher anti-cancer activities and had greater potential to interact with STAT3/CDK2/4/6 than did NSC765599 with an open-ring structure. NSC765690 and NSC765599 met the required safety and criteria of a good drug candidate, and are thus worthy of further in-vitro and in-vivo investigations in tumor-bearing mice to assess their full therapeutic efficacy.

Vitamin D as Radiosensitizer: A Review in Cell Line -

2020 ◽  
Vol 10 (6) ◽  
pp. 315-324
Author(s):  
Fahmi Radityamurti ◽  
Fauzan Herdian ◽  
Tiara Bunga Mayang Permata ◽  
Handoko Handoko ◽  
Henry Kodrat ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cell Differentiation ◽  
Cell Line ◽  
Cell Lines ◽  
Anticancer Agent ◽  
Medical Literature ◽  
In Vitro Studies ◽  
Anti Cancer

Introduction: Vitamin D has been shown to have anti-cancer properties such as antioxidants, anti-proliferative, and cell differentiation. The property of vitamin D as an anticancer agent triggers researchers to find out whether vitamin D is useful as a radiosensitizer. Multiple studies have been carried out on cell lines in various types of cancer, but the benefits of vitamin D as a radiosensitizer still controversial. This paperwork aims to investigate the utilization of Vitamin D3 (Calcitriol) as radiosensitizer in various cell line through literature review.Methods: A systematic search of available medical literature databases was performed on in-vitro studies with Vitamin D as a radiosensitizer in all types of cell lines. A total of 11 in-vitro studies were evaluated.Results: Nine studies in this review showed a significant effect of Vitamin D as a radiosensitizer agent by promoting cytotoxic autophagy, increasing apoptosis, inhibiting of cell survival and proliferation, promoting gene in ReIB inhibition, inducing senescene and necrosis. The two remaining studies showed no significant effect in the radiosensitizing mechanism of Vitamin D due to lack of evidence in-vitro settings.Conclusion: Vitamin D have anticancer property and can be used as a radiosensitizer by imploring various mechanism pathways in various cell lines. Further research especially in-vivo settings need to be evaluated.

Synthesis of Some Novel Benzimidazole Derivatives as Anticancer Agent, and Evaluation for CDK2 Inhibition Activity

2021 ◽  
Vol 17 ◽  
Author(s):  
Rania Helmy Abd El-Hameed ◽  
Samar Said Fatahala ◽  
Amira Ibrahim Sayed
Keyword(s):  
Cell Lines ◽  
Docking Study ◽  
Binding Pocket ◽  
Kinase Assay ◽  
Benzimidazole Derivatives ◽  
Pharmacological Activities ◽  
Anticancer Compounds ◽  
Anti Cancer ◽  
Hct 116

Background: Thiobezimidazoles reveal various pharmacological activities due to similarities with many natural and synthetic molecules, they can easily interact with biomolecules of living systems. Objective: A series of substituted 2-thiobezimidazoles has been synthesized .Twelve final compounds were screened for in vitro anti-cancer activities against sixty different cell-lines. Methods: The spectral data of the synthesized compounds were characterized. Docking study for active anticancer compounds and CDK2/CyclinA2 Kinase assay against standard reference; Imatinib were performed. Results: Two compounds (3c&3l) from the examined series revealed effective antitumor activity in vitro against two-cancer cell lines (Colon Cancer (HCT-116) and Renal Cancer (TK-10). The docking study of synthesized molecules discovered a requisite binding pose in CDK-ATP binding pocket. 3c &3l were promoted in the CDK2/CyclinA2 Kinase assay against standard reference Imatinib. Conclusion: Against all tested compounds ; two compounds 3c &3l were found active against two types of cell-lines.

The Design and Synthesis of Novel Phenothiazine Derivatives as Potential Cytotoxic Agents

2019 ◽  
Vol 17 (1) ◽  
pp. 57-67
Author(s):  
Yepeng Luan ◽  
Jinyi Liu ◽  
Jianjun Gao ◽  
Jinhua Wang
Keyword(s):  
Cell Lines ◽  
High Efficiency ◽  
Human Cancer ◽  
Human Tumor ◽  
Cytotoxic Agents ◽  
Cancer Drug ◽  
Human Cancer Cell Lines ◽  
Incidence And Mortality ◽  
Anti Cancer

Background: Cancer incidence and mortality have been increasing and cancer is still the leading cause of death all over the world. Despite the enormous progress in cancer treatment, many patients died of ineffective chemotherapy and drug resistance. Therefore, the design and development of anti-cancer drugs with high efficiency and low toxicity is still one of the most challenging tasks. Tricyclic heterocycles, such as phenothiazine, are always important sources of scaffolds for anti-cancer drug discovery. Methods: In this work, ten new urea-containing derivatives of phenothiazine coupled with different kinds of amine motifs at the endpoint through a three carbon long spacer were designed and synthesized. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR and HRMS. All the synthesized compounds were tested for their antitumor activity in vitro against the proliferation of PC-3 cells, and the compounds with best potency entered further cytotoxicity evaluations against other 22 human tumor cell lines. Mechanism was also studied. Results: From all data, it showed that among all 10 target compounds, TTi-2 showed the best effect in inhibiting the proliferation of 23 human cancer cell lines while TTi-2 without obvious inhibitory effect on normal cell. Furthermore, our results also showed that TTi-2 could inhibit migration, invasion and colony formation of MDA-MB-231 cells. Finally, TTi-2 can induce arrest of cell cycle at G0/G1 phase and cell apoptosis by activating the caspase 3 activity. Conclusion: All these results suggested that TTi-2 might be used as a promising lead compound for anticancer drug development.

scholarly journals Therapeutic Anticancer Uses of the Active Principles of “Rhopalurus junceus” Venom

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 382
Author(s):  
Mario Dioguardi ◽  
Giorgia Apollonia Caloro ◽  
Luigi Laino ◽  
Mario Alovisi ◽  
Diego Sovereto ◽  
...  
Keyword(s):  
Cell Lines ◽  
Carcinoma Cell ◽  
Meta Analysis ◽  
Scorpion Venom ◽  
In Vitro Studies ◽  
Active Components ◽  
Eligibility Criteria ◽  
Carcinoma Cell Lines ◽  
Anti Cancer

The Rhopalurus junceus is a scorpion belonging to the Buthidae family that finds its habitat in Cuba. This scorpion is known by the common name of “Blue Scorpion”. The venom is used on the island of Cuba as an alternative cure for cancer and, more recently, in the research of active components for biomedicine. Recently, the venom has been tested in several studies to investigate its effects on cancer cell lines, and the initial results of in vitro studies demonstrated how this poison can be effective on certain carcinoma cell lines (Hela, SiHa, Hep-2, NCI-H292, A549, MDA-MB-231, MDA-MB-468, and HT-29). The aim of this review is, therefore, to describe the effects of the venom on carcinoma lines and to investigate all anti-cancer properties studied in the literature. The research was conducted using four databases, Pub Med, Scopus, EBSCO, and Web of Science, through the use of keywords, by two independent reviewers following the PRISMA protocol, identifying 57 records. The results led to a total of 13 articles that met the eligibility criteria. The data extracted for the purpose of meta-analysis included the IC50 of the venom on carcinoma cell lines. The results of the meta-analysis provided a pooled mean of the IC50 of 0.645 mg/mL (95% CI: 0.557, 0.733), with a standard error (SE) = 0.045, p < 0.001. The analysis of the subgroups, differentiated by the type of cell line used, provided insight regarding how the scorpion venom was effective on the cell lines of lung origin (NCI-H292, A549, and MRC-5) with a pooled mean of IC50 0.460 mg/mL (95% CI: 0.290, 0.631) SE (0.087) p < 0.001. The results described in the literature for in vitro studies are encouraging, and further investigations should be carried out and deepened.

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