Safe and Effective Kinase Inhibitors for the Treatment of Gynecological Cancers: In Silico Approach

2021 ◽  
Vol 22 ◽  
Author(s):  
Vaishali M. Patil ◽  
Abhishek Kumar ◽  
Vaishali Anand ◽  
Priya Bansal ◽  
Neeraj Masand
Keyword(s):  
Mortality Rate ◽  
Anticancer Agents ◽  
In Silico ◽  
Kinase Inhibitors ◽  
Developmental Toxicity ◽  
Reproductive Toxicity ◽  
Cancer Therapeutics ◽  
Cancer Drugs ◽  
Gynecological Cancers ◽  
Anti Cancer

Aims: To study various types of gynecological cancers and the available therapeutics to investigate safe and effective drugs. Background: Cancer is the most common cause of mortality throughout the world. When the statistics is considered for gynecological cancers, ovarian, cervical and uterine cancers are among the most prevalent types. They have worst prognosis and the highest mortality rate and by the year 2040 significant increase in mortality rate is predicted. Objective: The major limitation with development of anti-cancer therapeutics for the gynecological cancers are safety of the therapeutics for the developing fetus as well as the mother. Various medicinal classes of natural to synthetic therapeutics have been reported including kinase inhibitors as the most promising category of anti-cancer drugs. Method: A dataset of kinase inhibitory clinically approved anticancer agents was derived through literature review. A QSAR based approach i.e. VEGAQSAR has been applied to evaluate the reproductive and developmental toxicity for the selected class of kinase inhibitors. Result: In the present work, the promising category of anticancer kinase inhibitors has been investigated for its toxicity potential with the help of in silico approach. The anti-cancer kinase inhibitors were categorized based on the found non-toxic or toxic properties towards reproductive and developmental toxicity. Conclusion: Early prediction of the available or proposed anti-cancer therapeutics for their contribution towards developmental and reproductive toxicity is an important criterion for their use in pregnancy associated cancers. The investigation of toxicity profile of available anti-cancer kinase therapeutics will be helpful to design and develop novel and safe anti-cancer drugs in the near future. Other: The study outcomes will benefit the current anticancer drug development efforts.

Nitrogen-Containing Heterocycles as Anticancer Agents: An Overview

2020 ◽  
Vol 20 (18) ◽  
pp. 2150-2168 ◽  
Author(s):  
Damanpreet K. Lang ◽  
Rajwinder Kaur ◽  
Rashmi Arora ◽  
Balraj Saini ◽  
Sandeep Arora
Keyword(s):  
Side Effects ◽  
Anticancer Agents ◽  
Kinase Inhibitors ◽  
Building Blocks ◽  
Basic Structure ◽  
Present Review ◽  
Cancer Drugs ◽  
Biological Compounds ◽  
Anti Cancer ◽  
Structural Search

Background: Cancer is spreading all over the world, and it is becoming the leading cause of major deaths. Today’s most difficult task for every researcher is to invent a new drug that can treat cancer with minimal side effects. Many factors, including pollution, modern lifestyle and food habits, exposure to oncogenic agents or radiations, enhanced industrialization, etc. can cause cancer. Treatment of cancer is done by various methods that include chemotherapy, radiotherapy, surgery and immunotherapy in combination or singly along with kinase inhibitors. Most of the anti-cancer drugs use the concept of kinase inhibition. Objective: The number of drugs being used in chemotherapy has heterocycles as their basic structure in spite of various side effects. Medicinal chemists are focusing on nitrogen-containing heterocyclic compounds like pyrrole, pyrrolidine, pyridine, imidazole, pyrimidines, pyrazole, indole, quinoline, oxadiazole, azole, benzimidazole, etc. as the key building blocks to develop active biological compounds. The aim of this study is to attempt to compile a dataset of nitrogen-containing heterocyclic anti-cancer drugs. Methods: We adopted a structural search on notorious journal publication websites and electronic databases such as Bentham Science, Science Direct, PubMed, Scopus, USFDA, etc. for the collection of peer-reviewed research and review articles for the present review. The quality papers were retrieved, studied, categorized into different sections, analyzed and used for article writing. Conclusion: As per FDA databases, nitrogen-based heterocycles in the drug design are almost 60% of unique small-molecule drugs. Some of the nitrogen-containing heterocyclic anti-cancer drugs are Axitinib, Bosutinib, Cediranib, Dasatanib (Sprycel®), Erlotinib (Tarceva®), Gefitinib (Iressa®), Imatinib (Gleevec®), Lapatinib (Tykerb ®), Linifanib, Sorafenib (Nexavar®), Sunitinib (Sutent®), Tivozanib, etc. In the present review, we shall focus on the overview of nitrogen-containing heterocyclic active compounds as anti-cancer agents.

scholarly journals Anticancer Agents from Diverse Natural Sources

2014 ◽  
Vol 9 (11) ◽  
pp. 1934578X1400901 ◽  
Author(s):  
Jabeena Khazir ◽  
Darren L. Riley ◽  
Lynne A. Pilcher ◽  
Pieter De-Maayer ◽  
Bilal Ahmad Mir
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Anticancer Agents ◽  
Marine Organisms ◽  
New Drugs ◽  
Human Diseases ◽  
Cancer Drugs ◽  
Natural Sources ◽  
Anti Cancer ◽  
Ancient Times

This review attempts to portray the discovery and development of anticancer agents/drugs from diverse natural sources. Natural molecules from these natural sources including plants, microbes and marine organisms have been the basis of treatment of human diseases since the ancient times. Compounds derived from nature have been important sources of new drugs and also serve as templates for synthetic modification. Many successful anti-cancer drugs currently in use are naturally derived or their analogues and many more are under clinical trials. This review aims to highlight the invaluable role that natural products have played, and continue to play, in the discovery of anticancer agents.

scholarly journals Ethyl 4-(2-fluorophenyl)-6-methyl-2-thioxo-1-(p-tolyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Molbank ◽  
10.3390/m1029 ◽  
2018 ◽  
Vol 2018 (4) ◽  
pp. M1029 ◽  
Author(s):  
Itamar Gonçalves ◽  
Luciano Porto Kagami ◽  
Gustavo Machado das Neves ◽  
Liliana Rockenbach ◽  
Leonardo Davi ◽  
...  
Keyword(s):  
In Silico ◽  
Biginelli Reaction ◽  
Cancer Drugs ◽  
Biological Targets ◽  
In Silico Studies ◽  
Anti Cancer ◽  
Privileged Structure ◽  
Good Potential

The Biginelli reaction is a highly versatile reaction that leads to dihydropyrimidinones/thiones. This scaffold is reported as being a privileged structure due to its ability to interact with biological targets. Synthesis of ethyl 4-(2-fluorophenyl)-6-methyl-2-thioxo-1-(p-tolyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate was achieved through the Biginelli reaction using a functionalized thiourea. In silico studies demonstrated that the compound title showed good potential for interacting with ecto-5’-nucleotidase, which has been considered as a target in designs for anti-cancer drugs.

scholarly journals Brassicaceae-Derived Anticancer Agents: Towards a Green Approach to Beat Cancer

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 868 ◽  
Author(s):  
Luigi Mandrich ◽  
Emilia Caputo
Keyword(s):  
Anticancer Agents ◽  
Current Knowledge ◽  
Cancer Therapeutics ◽  
Cancer Treatments ◽  
Mortality And Morbidity ◽  
Green Approach ◽  
Anti Cancer ◽  
Brassica Vegetables ◽  
Health Promoting ◽  
Domestic Processing

Cancer is the main cause of mortality and morbidity worldwide. Although a large variety of therapeutic approaches have been developed and translated into clinical protocols, the toxic side effects of cancer treatments negatively impact patients, allowing cancer to grow. Brassica metabolites are emerging as new weapons for anti-cancer therapeutics. The beneficial role of the consumption of brassica vegetables, the most-used vegetables in the Mediterranean diet, particularly broccoli, in the prevention of chronic diseases, including cardiovascular diseases, diabetes, and obesity, has been well-documented. In this review, we discuss the anti-tumor effects of the bioactive compounds from Brassica vegetables with regard to the compounds and types of cancer against which they show activity, providing current knowledge on the anti-cancer effects of Brassica metabolites against major types of tumors. In addition, we discuss the impacts of industrial and domestic processing on the compounds’ functional properties before their consumption as well as the main strategies used to increase the content of health-promoting metabolites in Brassica plants through biofortification. Finally, the impacts of microbiota on the compounds’ bioactivity are considered. This information will be helpful for the further development of efficacious anti-cancer drugs.

Benzofuran-Based Estrogen Receptor α Modulators as Anti-Cancer Therapeutics: In Silico and Experimental Studies

2013 ◽  
Vol 20 (22) ◽  
pp. 2820-2837 ◽  
Author(s):  
Min Leow ◽  
Hui Li Chin ◽  
Peggy Yu ◽  
Kalyan Pasunooti ◽  
Raymond Xu Tay ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
In Silico ◽  
Experimental Studies ◽  
Cancer Therapeutics ◽  
Anti Cancer

Recent Progress in Histone Deacetylase Inhibitors as Anticancer Agents

2020 ◽  
Vol 27 (15) ◽  
pp. 2449-2493 ◽  
Author(s):  
Loredana Cappellacci ◽  
Diego R. Perinelli ◽  
Filippo Maggi ◽  
Mario Grifantini ◽  
Riccardo Petrelli
Keyword(s):  
Clinical Trials ◽  
Histone Deacetylase ◽  
Anticancer Agents ◽  
Histone Deacetylase Inhibitors ◽  
Cyclic Peptide ◽  
Hdac Inhibitors ◽  
Cancer Therapeutics ◽  
Rational Drug Design ◽  
Modeling Tools ◽  
Anti Cancer

Histone Deacetylase (HDAC) inhibitors are a relatively new class of anti-cancer agents that play important roles in epigenetic or non-epigenetic regulation, inducing death, apoptosis, and cell cycle arrest in cancer cells. Recently, their use has been clinically validated in cancer patients resulting in the approval by the FDA of four HDAC inhibitors, vorinostat, romidepsin, belinostat and panobinostat, used for the treatment of cutaneous/peripheral T-cell lymphoma and multiple myeloma. Many more HDAC inhibitors are at different stages of clinical development for the treatment of hematological malignancies as well as solid tumors. Also, clinical trials of several HDAC inhibitors for use as anti-cancer drugs (alone or in combination with other anti-cancer therapeutics) are ongoing. In the intensifying efforts to discover new, hopefully, more therapeutically efficacious HDAC inhibitors, molecular modelingbased rational drug design has played an important role. In this review, we summarize four major structural classes of HDAC inhibitors (hydroxamic acid derivatives, aminobenzamide, cyclic peptide and short-chain fatty acids) that are in clinical trials and different computer modeling tools available for their structural modifications as a guide to discover additional HDAC inhibitors with greater therapeutic utility.

scholarly journals Lipid Drug Carriers for Cancer Therapeutics: An Insight into Lymphatic Targeting, P-gp, CYP3A4 Modulation and Bioavailability Enhancement

2020 ◽  
Vol 10 (4) ◽  
pp. 524-541
Author(s):  
Shashank Chaturvedi ◽  
Anurag Verma ◽  
Vikas Anand Saharan
Keyword(s):  
Drug Exposure ◽  
Biological Membrane ◽  
Cancer Therapeutics ◽  
Drug Carriers ◽  
Cancer Drugs ◽  
Proliferating Cells ◽  
Bioavailability Enhancement ◽  
Glycoprotein P ◽  
Anti Cancer ◽  
Lymphatic Route

In the treatment of cancer, chemotherapy plays an important role though the efficacy of anticancer drug administered orally is limited, due to their poor solubility in physiological medium, inability to cross biological membrane, high Para-glycoprotein (P-gp) mediated drug efflux, and pre-systemic metabolism. These all factors cumulatively reduce drug exposure at the target site leading to multidrug resistance (MDR). Lipid based carriers systems has been explored to overcome solubility and permeability related issues of anti-cancer drugs. The lipid based formulations have also been reported to circumvent the effect of P-gp and CYP3A4. Further long chain triglycerides (LCT) has shown their ability to access Lymphatic route over Medium Chain Triglycerides, as the former has been extensively used for targeting anti-cancer drugs at proliferating cells through lymphatic route. Therefore this review tries to reflect the usefulness of lipid based drug carriers systems (viz. liposome, solid lipid nanoparticle, nano-lipid carriers, self-emulsifying, lipidic pro-drugs) in targeting lymphatic system and overcoming issues related to solubility and permeability of anti-cancer drugs. Moreover, we have also tried to reflect how critically lipid based carriers are important in maximizing therapeutic safety and efficacy of anti-cancer drugs.

scholarly journals Marine-Derived Natural Products as ATP-Competitive mTOR Kinase Inhibitors for Cancer Therapeutics

2021 ◽  
Vol 14 (3) ◽  
pp. 282
Author(s):  
Shraddha Parate ◽  
Vikas Kumar ◽  
Gihwan Lee ◽  
Shailima Rampogu ◽  
Jong Chan Hong ◽  
...  
Keyword(s):  
Natural Products ◽  
In Silico ◽  
Cellular Proliferation ◽  
Kinase Inhibitors ◽  
Binding Free Energy ◽  
Mammalian Target Of Rapamycin ◽  
Cancer Therapeutics ◽  
Mtor Inhibitors ◽  
Binding Pocket ◽  
Pharmacophore Modeling

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase portraying a quintessential role in cellular proliferation and survival. Aberrations in the mTOR signaling pathway have been reported in numerous cancers including thyroid, lung, gastric and ovarian cancer, thus making it a therapeutic target. To attain this objective, an in silico investigation was designed, employing a pharmacophore modeling approach. A structure-based pharmacophore (SBP) model exploiting the key features of a selective mTOR inhibitor, Torkinib directed at the ATP-binding pocket was generated. A Marine Natural Products (MNP) library was screened using SBP model as a query. The retrieved compounds after consequent drug-likeness filtration were subjected to molecular docking with mTOR, thus revealing four MNPs with better scores than Torkinib. Successive refinement via molecular dynamics simulations demonstrated that the hits formed crucial interactions with key residues of the pocket. Furthermore, the four identified hits exhibited good binding free energy scores through MM-PBSA calculations and the subsequent in silico toxicity assessments displayed three hits deemed essentially non-carcinogenic and non-mutagenic. The hits presented in this investigation could act as potent ATP-competitive mTOR inhibitors, representing a platform for the future discovery of drugs from marine natural origin.

Overview on Anticancer Drug Design and Development

2018 ◽  
Vol 25 (15) ◽  
pp. 1704-1719 ◽  
Author(s):  
Sureyya Olgen
Keyword(s):  
Kinase Inhibitors ◽  
Molecular Design ◽  
Resistance Mechanisms ◽  
Cancer Drug ◽  
Computational Techniques ◽  
Cancer Therapies ◽  
Cancer Drugs ◽  
Design Strategies ◽  
Advantages And Disadvantages ◽  
Anti Cancer

Background: Many impediments of current anti-cancer therapies have urged scientists to discover new agents. As a result of growing spectrums of new targets and strategies and recent biological and biotechnological progresses, many anti-cancer agents such as monoclonal antibodies, small molecule tyrosine kinase inhibitors and epigenetic drugs have been reached to clinical trials. Objectives: This review helps to understand the rationale for the development of inhibitors against major targets such as cell growth, proliferation, survival, angiogenesis and recent targets such as proteasome, heat shock proteins, and epigenetics. Methods: Recent approaches of the target-based anti-cancer drug developments were highlighted to giving some examples from approved agents. Many factors, such as metabolic change, hypoxia, cancer precursors and cancer resistant cells, and their effect on drug resistance mechanisms were discussed. The impacts of advanced computational techniques to identify targets of cancer and designing more selective inhibitors were explained. Results: Contributions of recent techniques such as a network analysis, the precise modes of action and computational methodologies especially simulation of bio-molecular processes to clarify targets, mechanism actions and reasons of lack of efficacy of anti-cancer drugs have been explained. The relationship between the several mechanisms and molecular design strategies has been discussed. Conclusion: This review provides an overview of important targets and design strategies of anti-cancer drugs, advantages and disadvantages of these methods and evaluation of some currently used anticancer targets in clinical studies.

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