DNA Interaction and Cytotoxic studies on Mono/Di-Oxo and Peroxo-Vanadium (V) complexes – A Review

2021 ◽  
Vol 21 ◽  
Author(s):  
Saraswathi Kothandan ◽  
Angappan Sheela
Keyword(s):  
Biological Significance ◽  
Protein Tyrosine Phosphatases ◽  
Dna Interaction ◽  
Chemotherapeutic Agents ◽  
Drug Candidate ◽  
Vanadium Complexes ◽  
Anticancer Activities ◽  
Antitumor Effects ◽  
Insulin Mimetic ◽  
Extracellular Regulated Kinase

: Vanadium is considered to be biologically significant and several vanadium IV & V complexes have successfully been studied as chemotherapeutic agents like insulin mimetic, antibacterial, antioxidant, and anticancer activities. The divergent ligand systems also play a pivotal role in designing the metal complex with desired properties. Thus, the combination of both with their synergistic advantages results in a potential drug candidate. Different mechanistic pathways have been proposed to explain the antitumor effects of vanadium complexes including induction of tyrosine residues phosphorylation, inhibition of key protein tyrosine phosphatases (PTPases) which in turn promote the activation of the extracellular regulated kinase cascading (ERK) pathway. In the current review, we have summarized the work on vanadium (V) complexes based on different ligand systems and their biological significance as an anticancer lead compound.

Synthesis and characterization of a new series of thiadiazole derivatives as potential anticancer agents

2020 ◽  
Vol 26 (1) ◽  
pp. 6-13 ◽  
Author(s):  
Ulviye Acar Çevik ◽  
Derya Osmaniye ◽  
Serkan Levent ◽  
Begüm Nurpelin Sağlik ◽  
Betül Kaya Çavuşoğlu ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Biological Activities ◽  
Cancer Cell Line ◽  
Chemotherapeutic Agents ◽  
Anticancer Activities ◽  
Normal Tissues ◽  
H Nmr ◽  
Wide Range ◽  
Thiadiazole Derivatives ◽  
Low Efficiency

AbstractCancer is one of the most common causes of death in the world. Despite the importance of combating cancer in healthcare systems and research centers, toxicity in normal tissues and the low efficiency of anticancer drugs are major problems in chemotherapy. Nowadays the aim of many medical research projects is to discover new safer and more effective anticancer agents. 1,3,4-Thiadiazole compounds are important fragments in medicinal chemistry because of their wide range of biological activities, including anticancer activities. The aim of this study was to determine the capacity of newly synthesized 1,3,4-thiadiazole compounds as chemotherapeutic agents. The structures of the obtained compounds were elucidated using 1H-NMR, 13C-NMR and mass spectrometry. Although the thiadiazole derivatives did not prove to be significantly cytotoxic to the tumour tissue cultures, compound 4i showed activity against the C6 rat brain cancer cell line (IC50 0.097 mM) at the tested concentrations.

Probiotics for the Chemoprotective Role Against the Toxic Effect of Cancer Chemotherapy

2021 ◽  
Vol 21 ◽  
Author(s):  
Aafrin Waziri ◽  
Charu Bharti ◽  
Mohammed Aslam ◽  
Parween Jamil ◽  
Aamir Mirza ◽  
...  
Keyword(s):  
Side Effects ◽  
Clinical Management ◽  
Clinical Evidence ◽  
Unmet Need ◽  
Chemotherapeutic Agents ◽  
Antitumor Effects ◽  
Anti Cancer ◽  
Different Types ◽  
Growth Promoting ◽  
High Degree

Background: The processes of chemo- and radiation therapy-based clinical management of different types of cancers are associated with toxicity and side effects of chemotherapeutic agents. So, there is always an unmet need to explore agents to reduce such risk factors. Among these, natural products have generated much attention because of their potent antioxidant and antitumor effects. In the past, some breakthrough outcomes established that various bacteria in the human intestinal gut are bearing growth-promoting attributes and suppressing the conversion of pro-carcinogens into carcinogens. Hence, probiotics integrated approaches are nowadays being explored as rationalized therapeutics in the clinical management of cancer. Methods: Here, published literature was explored to review chemoprotective roles of probiotics against toxic and side effects of chemotherapeutics. Results: Apart from excellent anti-cancer abilities, probiotics are bearing and alleviate toxicity and side effects of chemotherapeutics, with a high degree of safety and efficiency. Conclusion: Preclinical and clinical evidence suggested that due to the chemoprotective roles of probiotics against side effects and toxicity of chemotherapeutics, their integration in chemotherapy would be a judicious approach.

Natural-Derived Molecules as a Potential Adjuvant in Chemotherapy: Normal Cell Protectors and Cancer Cell Sensitizers

2021 ◽  
Vol 21 ◽  
Author(s):  
Rajib Hossain ◽  
Muhammad Torequl Islam ◽  
Mohammad S. Mubarak ◽  
Divya Jain ◽  
Rasel Khan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Side Effects ◽  
Cancer Cells ◽  
Chemotherapeutic Agents ◽  
Polyphenolic Compounds ◽  
Anticancer Effect ◽  
Anticancer Activities ◽  
Normal Cells ◽  
Anti Cancer ◽  
Global Threat

Background: Cancer is a global threat to humans and a leading cause of death worldwide. Cancer treatment includes, among other things, the use of chemotherapeutic agents, compounds that are vital for treating and preventing cancer. However, chemotherapeutic agents produce oxidative stress along with other side effects that would affect the human body. Objective: To reduce the oxidative stress of chemotherapeutic agents in cancer and normal cells by naturally derived compounds with anti-cancer properties, and protect normal cells from the oxidation process. Therefore, the need to develop more potent chemotherapeutics with fewer side effects has become increasingly important. Method: Recent literature dealing with the antioxidant and anticancer activities of the naturally naturally-derived compounds: morin, myricetin, malvidin, naringin, eriodictyol, isovitexin, daidzein, naringenin, chrysin, and fisetin has been surveyed and examined in this review. For this, data were gathered from different search engines, including Google Scholar, ScienceDirect, PubMed, Scopus, Web of Science, Scopus, and Scifinder, among others. Additionally, several patient offices such as WIPO, CIPO, and USPTO were consulted to obtain published articles related to these compounds. Result: Numerous plants contain flavonoids and polyphenolic compounds such as morin, myricetin, malvidin, naringin, eriodictyol, isovitexin, daidzein, naringenin, chrysin, and fisetin, which exhibit ‎antioxidant, anti-inflammatory, and anti-carcinogenic actions via several mechanisms. These compounds show sensitizers of cancer cells and protectors of healthy cells. Moreover, these compounds can reduce oxidative stress, which is accelerated by chemotherapeutics and exhibit a potent anticancer effect on cancer cells. Conclusions: Based on these findings, more research is recommended to explore and evaluate such flavonoids and polyphenolic compounds.

scholarly journals Biophysical Characterization and Anticancer Activities of Photosensitive Phytoanthraquinones Represented by Hypericin and Its Model Compounds

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5666
Author(s):  
Valéria Verebová ◽  
Jiří Beneš ◽  
Jana Staničová
Keyword(s):  
Photodynamic Therapy ◽  
Biological Activities ◽  
Chemical Properties ◽  
Physical And Chemical Properties ◽  
Anticancer Activities ◽  
Model Compounds ◽  
Antitumor Effects ◽  
Biophysical Characterization ◽  
Physical And Chemical ◽  
And Chemical Properties

Photosensitive compounds found in herbs have been reported in recent years as having a variety of interesting medicinal and biological activities. In this review, we focus on photosensitizers such as hypericin and its model compounds emodin, quinizarin, and danthron, which have antiviral, antifungal, antineoplastic, and antitumor effects. They can be utilized as potential agents in photodynamic therapy, especially in photodynamic therapy (PDT) for cancer. We aimed to give a comprehensive summary of the physical and chemical properties of these interesting molecules, emphasizing their mechanism of action in relation to their different interactions with biomacromolecules, specifically with DNA.

scholarly journals Identification of Potent VHZ Phosphatase Inhibitors with Structure-Based Virtual Screening

2012 ◽  
Vol 18 (2) ◽  
pp. 226-231 ◽  
Author(s):  
Hwangseo Park ◽  
So Ya Park ◽  
Jung Jin Oh ◽  
Seong Eon Ryu
Keyword(s):  
Virtual Screening ◽  
Active Site ◽  
Structural Features ◽  
Drug Candidate ◽  
The Novel ◽  
Anticancer Activities ◽  
Phosphatase Inhibitors ◽  
Structure Activity ◽  
Promising Target ◽  
Further Development

VH1-like phosphatase Z (VHZ) has proved to be a promising target for the development of therapeutics for the treatment of human cancers. Here, we report the first example for a successful application of structure-based virtual screening to identify the novel small-molecule inhibitors of VHZ. These inhibitors revealed high potencies with the associated IC50 values ranging from 3 to 20 µM and were also screened for having desirable physicochemical properties as a drug candidate. Therefore, they deserve consideration for further development by structure-activity relationship studies to optimize inhibitory and anticancer activities. Structural features relevant to the stabilization of the newly identified inhibitors in the active site of VHZ are discussed in detail.

scholarly journals The Multifaceted Roles of Pyroptotic Cell Death Pathways in Cancer

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1313
Author(s):  
Man Wang ◽  
Shuai Jiang ◽  
Yinfeng Zhang ◽  
Peifeng Li ◽  
Kun Wang
Keyword(s):  
Cell Death ◽  
Biological Significance ◽  
Chemotherapeutic Agents ◽  
The Body ◽  
Cell Swelling ◽  
Pathogen Invasion ◽  
Membrane Rupture ◽  
Cancer Management ◽  
Cell Death Pathways ◽  
Cancer Pathogenesis

Cancer is a category of diseases involving abnormal cell growth with the potential to invade other parts of the body. Chemotherapy is the most widely used first-line treatment for multiple forms of cancer. Chemotherapeutic agents act via targeting the cellular apoptotic pathway. However, cancer cells usually acquire chemoresistance, leading to poor outcomes in cancer patients. For that reason, it is imperative to discover other cell death pathways for improved cancer intervention. Pyroptosis is a new form of programmed cell death that commonly occurs upon pathogen invasion. Pyroptosis is marked by cell swelling and plasma membrane rupture, which results in the release of cytosolic contents into the extracellular space. Currently, pyroptosis is proposed to be an alternative mode of cell death in cancer treatment. Accumulating evidence shows that the key components of pyroptotic cell death pathways, including inflammasomes, gasdermins and pro-inflammatory cytokines, are involved in the initiation and progression of cancer. Interfering with pyroptotic cell death pathways may represent a promising therapeutic option for cancer management. In this review, we describe the current knowledge regarding the biological significance of pyroptotic cell death pathways in cancer pathogenesis and also discuss their potential therapeutic utility.

Celastrol Overcomes Chemoresistance in Vitro and Potentiates the Effect of Bortezomib Against Human Multiple Myeloma in Nude Mice Mode

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5017-5017
Author(s):  
Radhamani Kannaiyan ◽  
Manu Kanjoormana Aryan ◽  
Muthu K Shanmugam ◽  
Feng Li ◽  
Gautam Sethi
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Cell Lines ◽  
Nude Mice ◽  
Tumor Volume ◽  
Corn Oil ◽  
Conflicts Of Interest ◽  
Chemotherapeutic Agents ◽  
Antitumor Effects ◽  
Group I

Abstract Abstract 5017 Introduction: Multiple myeloma (MM) is a B cell malignancy characterized by clonal proliferation of B cell in the bone marrow with low proliferative index. Despite the advent of novel therapeutics in addition to conventional chemotherapeutics, MM remains incurable because of the development of chemoresistance. Persistent activation of NF-κB/STAT3 signaling pathways and deregulation of apoptosis is considered to play an important role in the development of chemoresistance. The use of anticancer drugs derived from natural sources may be able to overcome resistance without some of the debilitating side effects of conventional chemotherapy. Celastrol is one such compound that has gained substantial attention recently for its anti-inflammatory and anticancer activities and is derived from the Chinese medicinal plant ‘Tripterygium wilfordii. We have demonstrated that celastrol overcomes the chemoresistance and induce apoptosis in MM cells by inhibiting NF-κB and STAT 3 pathways cell lines sensitive and resistant to various chemotherapeutic agents and Bortezomib. Our experimental findings have indicated that celastrol in combination with bortezomib/thalidomide can inhibit proliferation, induce apoptosis and overcome chemoresistance in MM cells in synergistic manner. We also observed that celastrol inhibited the activation of NF-κB and STAT3 and downregulated the expression of various genes involved in MM proliferation, survival and angiogenesis. Materials and Methods: Male athymic balb/c nude mice were implanted with 2×106 cells with either Human MM U266 cell lines subcutaneously. When tumors have reached more than 0. 3 cm in diameter, the mice were randomized into four groups. Group I (control) received corn oil 100 ul i. p. for five days a week, group II received 0. 25 mg/kg celastrol in 100ul corn oil for five days a week, group III received 0. 25 mg/kg bortezomib in 100 ul corn oil i. p. weekly and group IV received 0. 25mg/kg celastrol in 100 ul corn oil i. p. 5 days a week and 0. 25 mg/kg bortezomib in 100 ul corn oil i. p. weekly for 3 consecutive weeks. The tumor volume and body weight of the mice were monitored twice a week for the duration of the experiment. On completion of the treatment period, mice were euthanized by i. p. phentobarbital (40 mg/kg b. w) followed by cervical dislocation and then tumors were dissected and diameters measured. The tumor volume was calculated using the formula [L × W2]/2, where W and L are the width (short diameter) and the length (long diameter) of the tumor and the tumors were subjected to histological examination. Results: In the MM xenograft mice model, we observed that celastrol potentiated the antitumor effects of bortezomib and this correlated with significant suppression of NF-κB, STAT3, COX-2 and VEGF which was demonstrated by IHC. Overall, our data indicates that celastrol could be a potential therapeutic agent for the treatment of MM, especially in combination with the novel anti-myeloma agents. Disclosures: No relevant conflicts of interest to declare.

Use of the Microculture Kinetic Assay of Apoptosis to Determine Chemosensitivities of Leukemias

Blood ◽  
1998 ◽  
Vol 92 (3) ◽  
pp. 968-980
Author(s):  
Vladimir D. Kravtsov ◽  
John P. Greer ◽  
James A. Whitlock ◽  
Mark J. Koury
Keyword(s):  
Cell Lines ◽  
Leukemia Cell ◽  
Chemotherapeutic Agents ◽  
Leukemia Cells ◽  
Target Cells ◽  
Apoptotic Cells ◽  
Chemosensitivity Test ◽  
Antitumor Effects ◽  
Kinetic Assay ◽  
Specific Patient

Chemotherapeutic agents exert their antitumor effects by inducing apoptosis. The microculture kinetic (MiCK) assay provides an automated, continuous means of monitoring apoptosis in a cell population. We used the MiCK assay to determine the chemosensitivities of the human promyelocytic HL-60 and lymphoblastic CEM cell lines and leukemia cells freshly isolated from patients with acute nonlymphocytic (ANLL) or acute lymphocytic (ALL) leukemias. Continuous monitoring of apoptosis in the MiCK assay permits determination of the time to the maximum apoptosis (Tm) and its two components which are initiation time (Ti) and development time (Td). Duration of the three timing components of apoptosis varies from hours to days depending on the drug, drug concentration, and type of target cells. In the MiCK assay, the extent of apoptosis is reported in kinetic units of apoptosis. Kinetic units are determined by the slope of the curve created when optical density caused by cell blebbing is plotted as a function of time. Using the leukemia cell lines, we define the relationship between kinetic units determined by the MiCK assay and the percentage of morphologically apoptotic cells in the culture. Flow cytometry analysis of apoptosis in Annexin-V-fluorescein isothiocyanate–labeled preparations of HL-60 and CEM cells was also used to compare with data obtained by the MiCK assay. The feasibility of the MiCK assay of apoptosis as a chemosensitivity test was confirmed by its comparison with a 3H-thymidine incorporation assay. We show that samples from 10 ANLL and ALL patients patients tested for sensitivity to various doses of idarubicin (IDR), daunorubicin (DNR), or mitoxantrone (MTA) gave the same percentages of apoptotic cells when calculated by the MiCK assay as when determined by morphological analysis. The MiCK assay was used for dose-response analyses of the sensitivities to IDR, DNR, and MTA of leukemia cells from 4 other patients (2 ANLL and 2 ALL). The results from both cell lines and patient samples indicate that ANLL cells are more sensitive than ALL cells to all three of these chemotherapeutic agents. However, for individual patients the chemosensitivities varied significantly among the three chemotherapeutic agents. These varying responses to IDR, DNR, and MTA indicate that the MiCK assay results can be of potential use in designing a treatment regimen for a specific patient with acute leukemia. Among several drugs of presumed similar efficacy, the MiCK assay can permit the selection of the specific chemotherapeutic agent that causes the most apoptosis in the patient's leukemic cells. © 1998 by The American Society of Hematology.

scholarly journals Isocudraxanthone K Induces Growth Inhibition and Apoptosis in Oral Cancer Cells via Hypoxia Inducible Factor-1α

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Mee-Ran Shin ◽  
Hwa-Jeong Lee ◽  
Soo-Kyung Kang ◽  
Q-Schick Auh ◽  
Young-Man Lee ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Nuclear Translocation ◽  
Hypoxia Inducible Factor ◽  
Signal Transduction Pathway ◽  
Annexin V ◽  
Time Dependent ◽  
Drug Candidate ◽  
Root Bark ◽  
Dependent Manner ◽  
Antitumor Effects

Isocudraxanthone K (IK) is a novel, natural compound from a methanol extract of the root bark ofCudrania tricuspidata. It has not been shown previously that IK possessed antitumor activity. We investigated the antitumor effects and molecular mechanism of IK and related signal transduction pathway(s) in oral squamous cell carcinoma cells (OSCCCs). The MTT assay revealed that IK had an antiproliferative effect on OSCCCs, in a dose- and time-dependent manner. IK induced apoptosis in OSCCCs, as identified by a cell-cycle analysis, annexin V-FITC and propidium iodide staining, and the nuclear morphology in cell death. IK caused time-dependent phosphorylation of Akt, p38, and ERK (extracellular signal-regulated kinase). In addition, IK increased the cytosolic to nuclear translocation of nuclear factor-κB (NF-κB) p65 and the degradation and phosphorylation of IκB-αin HN4 and HN12 cells. Furthermore, IK treatment downregulated hypoxia-inducible factor 1α(HIF-1α) and its target gene, vascular endothelial growth factor (VEGF). Cobalt chloride (CoCl2), a HIF-1αactivator, attenuated the IK-induced growth-inhibiting and apoptosis-inducing effects, and blocked IK-induced expression of apoptosis regulatory proteins, such as Bax, Bcl-2, caspase-3, caspase-8, and caspase-9, and cytochrome c. Collectively, these data provide the first evidence of antiproliferative and apoptosis-inducing effects of IK as a HIF-1αinhibitor and suggest it may be a drug candidate for chemotherapy against oral cancer.

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