scholarly journals Novel selective anticancer agents based on Sn and Au complexes. Mini-review

2020 ◽  
Vol 92 (8) ◽  
pp. 1201-1216
Author(s):  
Elena R. Milaeva ◽  
Dmitry B. Shpakovsky ◽  
Yulia A. Gracheva ◽  
Taisiya A. Antonenko ◽  
Tatyana D. Ksenofontova ◽  
...  
Keyword(s):  
Side Effects ◽  
Anticancer Agents ◽  
Antitumor Agents ◽  
Inorganic Compounds ◽  
Acquired Resistance ◽  
Cytotoxic Action ◽  
Mitochondrial Potential ◽  
Anti Cancer ◽  
Gold Compounds

AbstractCancer is one of the most common causes of death in modern medicine. Molecular design of novel substances with pharmacological activity is one of the goals of medicinal inorganic chemistry. Platinum complexes are widely used in the treatment of cancer, despite high efficacy their use is limited by side effects, as well as primary or acquired resistance. In this regard, the search for novel metal-containing antitumor compounds is underway. Organotins and gold compounds are promising pharmacological agents with anti-cancer properties. The introduction of protective antioxidant fragments into inorganic compounds molecules is a way to reduce the side effects of anti-cancer drugs on healthy cells. 2,6-dialkylphenols belonging to vitamin E (α-tocopherol) mimetics are widely used as antioxidants and stabilizers. The properties of Ph3SnCl (Sn-I), Ph3PAuCl (Au-I) and complexes Ph3SnSR (Sn-II) and Ph3PAuSR (Au-II) based on 2,6-di-tert-butyl-4-mercaptophenol (RSH) as radical scavengers and reducing agents were studied in model reactions. For Sn-II and Au-II the comparative study of cytotoxic action was made and the IC50 values on different cancer cell lines were found to be depended on the nature of metal. In general, Sn(IV) complexes possessed higher cytotoxicity than Au(I) complexes. In order to clarify the mechanism of cytotoxic mode of action the effect of compounds on Fe3+-induced lipid peroxidation, mitochondrial potential and mitochondrial permeability, cell cycle and induction of apoptosis was studied. Organotin compounds can bind tubulin SH-groups and inhibit its polymerization by a dose-dependent mechanism, whereas gold compounds inhibit Thioredoxin reductase (TrxR). In vivo experiments on acute toxicity of Sn-II and Au-II proved their moderate toxic action that opens prospects for the further study as antitumor agents.

Ursolic and Oleanolic Acids as Potential Anticancer Agents Acting in the Gastrointestinal Tract

2018 ◽  
Vol 16 (1) ◽  
pp. 78-91 ◽  
Author(s):  
Mateusz Pięt ◽  
Roman Paduch
Keyword(s):  
Gastrointestinal Tract ◽  
Side Effects ◽  
Anticancer Agents ◽  
In Vivo Studies ◽  
Pentacyclic Triterpenoids ◽  
Liver Cancers ◽  
Anti Cancer ◽  
Tumorigenic Activity

Background:Cancer is one of the main causes of death worldwide. Contemporary therapies, including chemo- and radiotherapy, are burdened with severe side effects. Thus, there exists an urgent need to develop therapies that would be less devastating to the patient’s body. Such novel approaches can be based on the anti-tumorigenic activity of particular compounds or may involve sensitizing cells to chemotherapy and radiotherapy or reducing the side-effects of regular treatment.Objective:Natural-derived compounds are becoming more and more popular in cancer research. Examples of such substances are Ursolic Acid (UA) and Oleanolic Acid (OA), plant-derived pentacyclic triterpenoids which possess numerous beneficial properties, including anti-tumorigenic activity.Results:In recent years, ursolic and oleanolic acids have been demonstrated to exert a range of anticancer effects on various types of tumors. These compounds inhibit the viability and proliferation of cancer cells, prevent their migration and metastasis and induce their apoptosis. Both in vitro and in vivo studies indicate that UA and OA are promising anti-cancer agents that can prevent carcinogenesis at each step. Furthermore, cancers at all stages are susceptible to the activity of these compounds. </P><P> Neoplasms that are formed in the gastrointestinal tract, i.e. gastric, colorectal, pancreatic, and liver cancers, are among the most common and most lethal malignancies. Their localization in the digestive system, however, facilitates the action of orally-administered (potential) anti-cancer agents, making chemopreventive drugs more accessible.In this paper, the anti-tumorigenic effect of ursolic and oleanolic acids on gastric, colon, pancreatic, and liver cancers, as well as the mechanisms underlying this process, are presented.

Novel Hybrid Compound 4-[(E)-2-phenylethenesulfonamido]-N-hydroxybutanamide with Antimetastatic and Cytotoxic Action: Synthesis and Anticancer Screening

2019 ◽  
Vol 18 (10) ◽  
pp. 1495-1504 ◽  
Author(s):  
Yurii L. Zborovskii ◽  
Viktor V. Orysyk ◽  
Iuliia Golovynska ◽  
Olena I. Dzhus ◽  
Liudmyla V. Garmanchuk ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Antitumor Agents ◽  
Morphological Properties ◽  
Cytotoxic Action ◽  
Adhesive Properties ◽  
Hybrid Compound ◽  
Antiproliferative Agent ◽  
High Fraction

Background: One of the most promising strategies to develop multi-targeted anticancer therapeutics is to introduce to the structure of a potential drug two or more pharmacophores (functional groups or structural fragments), which have antiproliferative, proapoptotic or antimetastatic properties acting via different mechanisms. Objective: To design, synthesize and perform screening of a novel hybrid anticancer compound. Method: A novel hybrid compound 4-[(E)-2-phenylethenesulfonamido]-N-hydroxybutanamide, combining butanehydroxamate and styrenesulfonamide moieties, was designed, synthesized and investigated as a potent antimetastatic and antiproliferative agent. The structure and purity of the synthesized compound were confirmed by 1H NMR, 13C NMR, LC/MS spectroscopy and elemental analysis. The compound was screened for the anticancer activity in vitro against HeLa and in vivo against Lewis lung carcinoma tumor, using an antitumor metalloenzyme inhibitor GM6001 (Ilomastat, Galardin) and Pifithrin-μ as control anticancer agents. Results: It was found that the application of our compound resulted in a high fraction of apoptotic cells in the cell population, along with disruption in the cell cycle profile manifested as arrest of proliferative phases. Furthermore, changes of the morphological properties (i.e., an enhancement of adhesive properties and reduction of the nuclear-to-cytoplasm ratio) were found. The in vivo screening revealed that the compound significantly inhibited the metastasizing process that was manifested by a reduction in the number and volume of metastases. Conclusions: The obtained results demonstrate that our compound can serve as a base for further structure optimization in order to design new highly-effective antimetastatic and antitumor agents.

Current Status and Future Perspective for Research on Medicinal Plants with Anticancerous Activity and Minimum Cytotoxic Value

2019 ◽  
Vol 20 (12) ◽  
pp. 1227-1243
Author(s):  
Hina Qamar ◽  
Sumbul Rehman ◽  
D.K. Chauhan
Keyword(s):  
Side Effects ◽  
Medicinal Plants ◽  
Anticancer Agents ◽  
Drug Targets ◽  
Psidium Guajava ◽  
Current Status ◽  
Future Perspective ◽  
Wide Range

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.

Nitrogen Mustards as Alkylating Agents: A Review on Chemistry, Mechanism of Action and Current USFDA Status of Drugs

2019 ◽  
Vol 19 (9) ◽  
pp. 1080-1102 ◽  
Author(s):  
Ghansham S. More ◽  
Asha B. Thomas ◽  
Sohan S. Chitlange ◽  
Rabindra K. Nanda ◽  
Rahul L. Gajbhiye
Keyword(s):  
Side Effects ◽  
Mechanism Of Action ◽  
Anticancer Agents ◽  
Nitrogen Mustard ◽  
Alkylating Agents ◽  
Cross Linking ◽  
Nitrogen Mustards ◽  
Information Leaflets ◽  
Anti Cancer ◽  
Approved Drugs

Background & Objective: :Nitrogen mustard derivatives form one of the major classes of anti-cancer agents in USFDA approved drugs list. These are polyfunctional alkylating agents which are distinguished by a unique mechanism of adduct formation with DNA involving cross-linking between guanine N-7 of one strand of DNA with the other. The generated cross-linking is irreversible and leads to cell apoptosis. Hence it is of great interest to explore this class of anticancer alkylating agents.Methods::An exhaustive list of reviews, research articles, patents, books, patient information leaflets, and orange book is presented and the contents related to nitrogen mustard anti-cancer agents have been reviewed. Attempts are made to present synthesis schemes in a simplified manner. The mechanism of action of the drugs and their side effects are also systematically elaborated.Results::This review provides a platform for understanding all aspects of such drugs right from synthesis to their mechanism of action and side effects, and lists USFDA approved ANDA players among alkylating anticancer agents in the current market.Conclusion: :Perusing this article, generic scientists will be able to access literature information in this domain easily to gain insight into the nitrogen mustard alkylating agents for further ANDA development. It will help the scientific and research community to continue their pursuit for the design of newer and novel heterocyclic alkylating agents of this class in the coming future.

scholarly journals Schiff Base Metal Complexes as Anticancer Agents

2019 ◽  
Vol 31 (3) ◽  
pp. 493-504 ◽  
Author(s):  
G. Sridevi ◽  
S. Arul Antony ◽  
R. Angayarkani
Keyword(s):  
Schiff Base ◽  
Anticancer Agents ◽  
Anticancer Agent ◽  
Antitumor Agents ◽  
Transition Metal Complex ◽  
Bioinorganic Chemistry ◽  
Structural Data ◽  
Ligand Substitution ◽  
Schiff Base Metal Complexes

Cutting-edge practices in bioinorganic chemistry are pivotal for enhancing the layout of compounds to lessen poisonous facet effect and recognize their mechanism of action. A powerful anticancer agent should own inherent, inhibitory property and also delivery, dosage and residence time in vivo. Organic function and conformation of mutated gene may be altered by way of binding of metal ions. Upswing of activities counting on the structural data, intending in enhancing and growing different forms of metal based compounds, continuous seek of extra metal based compounds have been synthesized via revamping the prevailing chemical shape via ligand substitution. The prevailing paper addresses the trendy development in the design of novel antitumor agents primarily based on transition metal complex via highlighting the near dating among their structural alternatives and cytotoxic ability.

scholarly journals Nitric oxide-dependent inflammation underlies Notch and PI3K/Akt oncogene cooperation

2017 ◽  
Author(s):  
Santiago Nahuel Villegas ◽  
Rita Gombos ◽  
Irene Gutiérrez Pérez ◽  
Lucia García López ◽  
Jesús García-Castillo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Side Effects ◽  
Activating Mutations ◽  
Genetic Inactivation ◽  
Multiple Organs ◽  
Anti Cancer ◽  
Therapeutic Development ◽  
Direct Targeting ◽  
Oxide Synthase

AbstractConcurrent activating mutations of the Notch and PI3K/Akt signalling pathways cooperate in the induction of aggressive cancers. Unfortunately, direct targeting of any of these aberrant pathways can result in severe side effects due to their broad physiological roles in multiple organs. Here, using an unbiased chemical in vivo screen in Drosophila we identified compounds that suppress the activity of the pro-inflammatory enzymes, nitric oxide synthase (NOS) and lipoxygenase (LOX), capable to block oncogenic Notch-PI3K/Akt cooperation without unwanted side effects. Genetic inactivation of NOS and LOX signalling components mirrors the anti-tumorigenic effect of the hit compounds. We show that NOS activity and immunosuppression associated to inflammation facilitates Notch-mediated tumorigenesis. Our study reveals an unnoticed immune inflammatory process underlying Notch-PI3K/Akt tumours and exposes NOS as a druggable target for anti-cancer therapeutic development.

scholarly journals Bioorthogonal Photo-Catalytic Activation of an Anti-Cancer Prodrug by Riboflavin

2021 ◽  
Author(s):  
Xin Yang ◽  
Limin Ma ◽  
Hongwei Shao ◽  
Xia Ling ◽  
Mengyu Yao ◽  
...  
Keyword(s):  
Side Effects ◽  
Cancer Treatment ◽  
Density Functional ◽  
Cancer Drug ◽  
Spatiotemporal Resolution ◽  
Precise Control ◽  
Catalytic Activation ◽  
Anti Cancer

Chemotherapies for cancer treatment usually suffer from poor targeting ability and serious side-effects. To improve the treatment efficiency and reduce side effects, photoactivatable chemotherapy has been recently proposed for precise cancer treatment with high spatiotemporal resolution. However, most photoactivatable prodrugs require decoration by stoichiometric photo-cleavable groups, which are only responsive to ultraviolet irradiation and suffer from low reaction efficiency. To tackle these challenges, we herein propose a bioorthogonal photo-catalytic activation strategy with riboflavin as the catalyst for in situ transformation of prodrug dihydrochelerythrine (DHCHE) prodrug into anti-cancer drug chelerythrine (CHE), which can efficiently kill cancer cells and inhibit in vivo tumor growth under light irradiation. Meanwhile, the photo-catalytic transformation from DHCHE into CHE was in situ monitored by green-to-red fluorescence conversion, which can be used for precise control of the therapeutic dose. The photocatalytic mechanism was also fully explored by means of density functional theory (DFT) calculations. We believe this imaging-guided bioorthogonal photo-catalytic activation strategy is promising for cancer chemotherapy in clinical applications.

scholarly journals Design, Synthesis, and Biological Evaluation of Novel Nitrogen Heterocycle-Containing Ursolic Acid Analogs as Antitumor Agents

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 877 ◽  
Author(s):  
Wenzhi Wang ◽  
Lei Lei ◽  
Zhi Liu ◽  
Hongbo Wang ◽  
Qingguo Meng
Keyword(s):  
Cell Lines ◽  
Ursolic Acid ◽  
Antitumor Agents ◽  
Biological Evaluation ◽  
Nitrogen Heterocycle ◽  
Mitochondrial Potential ◽  
Design Synthesis ◽  
Induced Apoptosis ◽  
Mkn45 Cell

Nineteen ursolic acid analogues were designed, synthesized, and evaluated for their antiproliferative activity against the Hela and MKN45 cell lines. Some compounds containing a piperazine moiety displayed moderate to high levels of antitumor activities against the tested cancer cell lines. The most potent compound shares the IC50 value of 2.1 µM and 2.6 µM for the Hela and MKN45 cell lines, respectively. Further mechanism studies and in vivo antitumor studies have shown that it decreased the apoptosis regulator (BCL2/BAX) ratio, disrupted mitochondrial potential and induced apoptosis, and suppressed the growth of Hela xenografts in nude mice.

Progress and development of C-3, C-6, and N-9 position substituted carbazole integrated molecular hybrid molecules as potential anticancer agents

2021 ◽  
Vol 21 ◽  
Author(s):  
Pratibha Mehta Luthra ◽  
Nitin Kumar
Keyword(s):  
Biological Activity ◽  
Side Effects ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Structural Motif ◽  
Hybrid Compounds ◽  
Hybrid Molecules ◽  
Anticancer Mechanism ◽  
Pharmacologically Active

Abstract: The carbazole skeleton, a key structural motif occurring naturally or chemically synthesized, have shown various biological activities. Molecular hybridization based on the combination of two or more bioactive pharmacophores has been an important tool to convert the potent structural leads to form new hybrid compounds with improved biological activity. In recent years, modifications/substitutions of the carbazole motif at C3, C6, N9 position have been carried to develop novel carbazole based potential anticancer agents in the cancer therapy. In the last fifteen years, several compounds based on carbazole core integrated to pharmacologically active molecular hybrid having active pharmacophore such as 1,3,4-thiadiazole, thiazole, guanidine, sulfonamides, glyoxamides, imidazole, phenanthrene, rhodamine, chalcones, imidazopyridine, platinum 2H-chromen-2-one, hydrazones, piperazine, Isoxazole-thiadiazole, pyrazole etc. have been synthesized showing anticancer profile at sub-micromolar to nano-molar concentrations. We have thoroughly reviewed the design, progress and development of C-3, C-6, and N-9 position substituted carbazole derivatives integrated with various medicinally active pharmacophore as potential anticancer agents evaluated against various cancer cell lines. Additionally, the anticancer mechanism and in vivo activity of the reported compounds have been discussed. This study will support in designing of a new pharmacophore that can be linked to carbazole motif for development for new, potent and target specific anticancer drugs with improved pharmacokinetics and minimal side effects.

Prominent Enhancement of Cisplatin Efficacy with Optimized Methoxy Poly(ethylene glycol)-Polycaprolactone Block Copolymeric Nanoparticles

2020 ◽  
Vol 16 (3) ◽  
pp. 335-343
Author(s):  
Ying-Tzu Yen ◽  
Xinyue Wang ◽  
Huan Zhang ◽  
Chun Wang ◽  
Zitong Lin ◽  
...  
Keyword(s):  
Side Effects ◽  
Anticancer Agents ◽  
Drug Carrier ◽  
Poly Ethylene Glycol ◽  
Therapeutic Concentration ◽  
Physical Chemical ◽  
Positron Emission ◽  
Pet Ct ◽  
Poly Ethylene

Chemotherapy has been one of the major standard treatments for a variety of cancers. cis-Dichlorodiamminoplatiunum (II) (cisplatin, CDDP), as one of the anticancer agents, demonstrated excellent efficacy against tumor and has been an indispensable component in chemotherapy, chemoradiation, chemo-molecular targeted therapy and chemo-immunotherapy. However, its therapeutic concentration was limited since its inevitable toxicity. Previously, we have constructed CDDPloaded nanoparticles (NPs) with mixture of poly(ethyleneglycol)-polycaprolactone (PEG-PCL) and polycarprolactone (HOPCL) by a facile method. The most optimal proportion of the two copolymers was selected through a series of physical, chemical, cytological and histological evaluations. In the present study, we explored the mechanisms of NPs and observed the in vivo antitumor effect after administrating CDDP-loaded PEG-PCL NPs. Positron emission tomography as well as computed tomography (PET/CT) were adopted for detecting tumoral metabolic activity. Images from fluorescence microscope revealed superior cellular uptake of CDDP-loaded NPs with rhodamine B aggregated intracellularly in cancer cells. Similar apoptotic rates between free CDDP group and CDDP-loaded NPs group was measured by flow cytometry. Tumor volumes and murine weights confirmed the superiority of CDDP-loaded NPs in therapeutic efficacy as compared with free CDDP. Blood tests showed milder side effects in CDDP-loaded nanoparticle group. PET/CT images illustrated less uptake intensity of FDG in mice received CDDP-loaded NPs than free CDDP. Our results suggest that PEG-PCL/PCL NPs could be a promising antitumor drug carrier for CDDP delivery with solid efficacy and minor side effects.

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