N-Alkylation of Anthracycline Antibiotics by Natural Sesquiterpene Lactones as a Way to Obtain Antitumor Agents with Reduced Side Effects

Anthracycline antitumor antibiotics are one of the promising classes of chemotherapeutic agents for cancer treatment. The main deterrent to their use is high toxicity to a healthy environment, including cumulative cardiotoxicity. In our work, bipharmacophore molecules containing in their structure a fragment of the known anthracycline antibiotics daunorubicin and doxorubicin and natural sesquiterpene lactones were obtained for the first time. When studying the biological activity of the synthesized compounds, it was found that with equal and, in some cases, higher cytotoxicity and glycolysis inhibition by anthracycline antibiotics conjugates with sesquiterpene lactones in comparison with doxo- and daunorubicin, a reduced damaging effect on the functioning of rat heart mitochondria was observed. The results obtained allow us to confirm the assumption that the chemical modification of the anthracycline antibiotics molecules doxo- and daunorubicin by natural sesquiterpene lactones can be a promising strategy for creating potential antitumor chemotherapeutic drugs with a pronounced cytotoxic effect on tumor cells and a reduced damaging effect on healthy cells of the human organism.

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Hepatotoxicity of chemotherapeutic agents: current state of the problem

Russian Journal of Oncology ◽

10.18821/1028-9984-2016-21-6-325-333 ◽

2016 ◽

Vol 21 (6) ◽

pp. 325-333

Author(s):

M. T Vatutin ◽

E. V Sklyannaya ◽

Mariam A. El-Khatib ◽

S. V Starchenko ◽

M. V Makarova

Keyword(s):

Kinase Inhibitors ◽

Antitumor Agents ◽

Opportunistic Infections ◽

Alkylating Agents ◽

Chemotherapeutic Agents ◽

Protein Kinase Inhibitors ◽

Drug Induced ◽

Anthracycline Antibiotics ◽

Current State ◽

High Level

This review is devoted to the actual for the present day problem of the hepatotoxicity of chemotherapeutic agents. Liver is the most important organ essential for the maintaining of the body’s internal environment. For the present time there is observed the high level of the morbidity and mortality rate against the background of drug-induced liver lesions due to, in the first instance, the lack ofproper manner for the substitution of the liver function but transplantation. Liver deteriorations due to the administration of antitumor agents have no pathognomonic clinical or histological features that significantly embarrasses the execution of the differential diagnosis with liver disorders against the background of administration of other preparations, either associated with opportunistic infections or the progression of previously acquired pathology of the liver. In the article there is described the toxic influence on the liver of most often used in oncology chemotherapeutic agents - antimetabolites, alkylating agents, platinum compounds, epothilones, taxanes, vinca alkaloids, monoclonal antibodies, anthracycline antibiotics, topoisomerase and protein kinase inhibitors is described in this article. In the review there are summarized results of recent studies of etiology, pathogenesis, clinical features, diagnosis, prevention and treatment of chemotherapy induced hepatotoxicity. The special attention is given to recent discoveries in the area of pathogenesis of chemotherapy induced hepatotoxicity. However many moments remain to be still not studied completely, that offers perspectives for further research in this field.

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Rhenium(I) Complexes with Pincer Ligands as a New Class of Potential Antitumor Agents

Proceedings ◽

10.3390/proceedings2019022043 ◽

2019 ◽

Vol 22 (1) ◽

pp. 43

Author(s):

Diana V. Aleksanyan ◽

Svetlana G. Churusova ◽

Ekaterina Yu. Rybalkina ◽

Vladimir A. Kozlov

Keyword(s):

Metal Complexes ◽

Antitumor Agents ◽

Solid Phase ◽

Organometallic Compounds ◽

Chemotherapeutic Agents ◽

Palladium Complexes ◽

Pincer Ligands ◽

New Class ◽

Solvent Free Conditions ◽

Potential Antitumor

Transition metal complexes attract continuous research interest as potential antitumor agents. The most popular compounds are ruthenium, gold, titanium, osmium, iridium, zinc, and palladium complexes, which have already displayed cytotoxic features that are not typical for classical platinum-containing chemotherapeutic agents. Substantially lower attention is drawn to organometallic compounds of rhenium. However, the known examples of cytotoxic organometallic rhenium derivatives with bidentate heterocyclic, organophosphorus, labile alkoxide, and hydroxide ligands render further studies in this field very promising. As for their analogs with multidentate ligands, a literature survey has revealed only a few examples of cytotoxic rhenium complexes, whereas the antitumor activity of cyclometallated derivatives has not been studied at all. At the same time, it is known that the use of pincer-type ligands having specific tridentate monoanionic frameworks, which offer multiple options for directed structural modifications, allows one to finely tune the thermodynamic and kinetic stability of the resulting metal complexes. Therefore, we synthesized and studied the cytotoxic properties of a series of rhenium(I) complexes with tridentate pincer-type ligands based on functionalized carboxamides bearing ancillary donor groups both in the acid and amine components. It was shown that the target complexes can be obtained not only by the conventional solution-based method, but also under solvent-free conditions according to the solid-phase methodology recently developed in our group. The results obtained were used to define the main structure–activity relationships for a principally new class of potential antitumor agents and to choose the most promising compounds for further studies in order to create new pharmaceuticals.

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Synthesis and in vitro evaluation of naphthalimide–benzimidazole conjugates as potential antitumor agents

Organic & Biomolecular Chemistry ◽

10.1039/c8ob02973c ◽

2019 ◽

Vol 17 (21) ◽

pp. 5349-5366 ◽

Cited By ~ 3

Author(s):

Iqubal Singh ◽

Vijay Luxami ◽

Kamaldeep Paul

Keyword(s):

Biological Activity ◽

Cell Lines ◽

Antitumor Agents ◽

Human Cancer ◽

Human Cancer Cell ◽

Human Cancer Cell Lines ◽

Cancer Types ◽

First Time ◽

Potential Antitumor

A novel series of benzimidazole-naphthalimide conjugates was synthesized for the first time and screened for in vitro biological activity for 60 human cancer cell lines representing nine different cancer types.

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Design, Synthesis of Novel Quinazolone Alkaloids Derivatives as Potential Antitumor Agents

Medicinal Chemistry ◽

10.2174/157340611796150987 ◽

2011 ◽

Vol 7 (4) ◽

pp. 295-300

Author(s):

Youguang Zheng ◽

Min Sun ◽

Yi Liu ◽

Mingdong Li ◽

Min Ji

Keyword(s):

Antitumor Agents ◽

Design Synthesis ◽

Potential Antitumor

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Synthesis and Biological Evaluation of Diaryl Ether Linked DC-81 Conjugates as Potential Antitumor Agents

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520613666131125122408 ◽

2013 ◽

Vol 13 (10) ◽

pp. 1590-1600 ◽

Cited By ~ 4

Author(s):

Ahmed Kamal ◽

A. Viswanath ◽

M. Ramaiah ◽

J. Murty ◽

Farheen Sultana ◽

...

Keyword(s):

Antitumor Agents ◽

Biological Evaluation ◽

Diaryl Ether ◽

Synthesis And Biological Evaluation ◽

Potential Antitumor

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A Review of Electroporation-based Antitumor Skin Therapies and Investigation of Betulinic Acid-loaded Ointment

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666171113120255 ◽

2018 ◽

Vol 18 (5) ◽

pp. 693-701

Author(s):

Monika Bakonyi ◽

Szilvia Berko ◽

Gabor Eros ◽

Gabor Varju ◽

Cristina A. Dehelean ◽

...

Keyword(s):

Betulinic Acid ◽

High Efficiency ◽

Antitumor Agents ◽

Ex Vivo ◽

Mouse Skin ◽

Chemotherapeutic Agents ◽

Hairless Mouse ◽

Promising Tool ◽

Acid Formulation ◽

Invasive Method

Background: Electrochemotherapy is a novel treatment for cutaneous and subcutaneous tumors utilizing the combination of electroporation and chemotherapeutic agents. Since tumors have an increasing incidence nowadays as a result of environmental and genetic factors, electrochemotherapy could be a promising treatment for cancer patients. Objective: The aim of this article is to summarize the novel knowledge about the use of electroporation for antitumor treatments and to present a new application of electrochemotherapy with a well-known plant derived antitumor drug betulinic acid. For the review we have searched the databases of scientific and medical research to collect the available publications about the use of electrochemotherapy in the treatment of various types of cancer. Method: By the utilization of the available knowledge, we investigated the effect of electroporation on the penetration of a topically applied betulinic acid formulation into the skin by ex vivo Raman spectroscopy on hairless mouse skin. Results: Raman measurements have demonstrated that the penetration depth of betulinic acid can be remarkably ameliorated by the use of electroporation, so this protocol can be a possibility for the treatment of deeper localized cancer nodules. Furthermore, it proved the influence of various treatment times, since they caused different spatial distributions of the drug in the skin. Conclusion: The review demonstrates that electrochemotherapy is a promising tool to treat different kinds of tumors with high efficiency and with only a few moderate adverse effects. Moreover, it presents a non-invasive method to enhance the penetration of antitumor agents, which can offer novel prospects for antitumor therapies.

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