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Processes
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Advances in Anticancer Agents
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Advances in Anticancer Agents

A special issue of Processes (ISSN 2227-9717). This special issue belongs to the section "Pharmaceutical Processes".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 28304

Special Issue Editors

Dr. Zdenek Kejik

E-Mail Website
Guest Editor
Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Kateřinská 32, 121 08 Prague 2, Czech Republic
Interests: tumor environment; metastatic activity; tumor proliferation; formulation of anticancer agents; drug delivery system; combination therapy; adjuvant therapy; neoadjuvant therapy; prevention of oncological diseases
Dr. Michal Masarik

E-Mail Website1 Website2
Guest Editor
Department of Pathological Physiology, Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice, 562500 Brno, Czech Republic
Interests: tumor biology; biochemistry and genetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite the enormous progress made in the last decade, many types of cancer lack effective therapeutic options. According to the World Health Organization, worldwide, 8 million human deaths per year (around 13% of all deaths) are caused by cancer. Therefore, new anticancer agents and novel strategies for their applications are being intensively developed and tested. It is becoming increasingly clear that a comprehensive approach is needed to overcome this obstacle. In addition to the cytostatic effect of anticancer drugs, it is necessary to target tumor proliferation and metastatic activity. Currently, several natural and synthetic agents with promising biological effects (e.g., the reduction of tumor invasiveness, aggressivity, and cancer risk) have been prepared and tested. However, their therapeutic effectivity can be strongly reduced by their pharmaceutically important properties, such as low solubility, cellular uptake chemical stability, or significant side effects and limited therapeutic effectivity. Nevertheless, their target transportation capabilities, formulations, and combination with other therapeutic regimens can be used to overcome some of these obstacles.

This Special Issue on “Advances in Anticancer Agents” aims to curate novel advances in the design, preparation/formulation, study, and application of natural and synthetic compounds to address longstanding challenges in their development and therapeutic applications. Topics include, but are not limited to, the following:

  • The design and study of molecular mechanisms of anticancer agents;
  • Strategy for the improvement of the therapeutic effectivity of anticancer agents;
  • Advantages and limitations of low/very low toxicity compounds for the prevention of oncological diseases;
  • The development and therapeutic applications of synthetic and natural compounds for adjuvant and neoadjuvant therapy.
Dr. Zdenek Kejik
Dr. Michal Masarik 
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Processes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • tumor environment
  • metastatic activity
  • tumor proliferation
  • formulation of anticancer agents
  • drug delivery system
  • combination therapy
  • adjuvant therapy
  • neoadjuvant therapy
  • prevention of oncological diseases

Published Papers (6 papers)

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Research

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16 pages, 2317 KiB  
Article
PPO-Inhibiting Herbicides and Structurally Relevant Schiff Bases: Evaluation of Inhibitory Activities against Human Protoporphyrinogen Oxidase
by Milan Jakubek, Michal Masařík, Tomáš Bříza, Robert Kaplánek, Kateřina Veselá, Nikita Abramenko and Pavel Martásek
Processes 2021, 9(2), 383; https://doi.org/10.3390/pr9020383 - 19 Feb 2021
Cited by 5 | Viewed by 3257
Abstract
The study of human protoporphyrinogen oxidase (hPPO) inhibition can contribute significantly to a better understanding of some pathogeneses (e.g., porphyria, herbicide exposure) and the development of anticancer agents. Therefore, we prepared new potential inhibitors with Schiff base structural motifs (2-hydroxybenzaldehyde-based Schiff bases 9 [...] Read more.
The study of human protoporphyrinogen oxidase (hPPO) inhibition can contribute significantly to a better understanding of some pathogeneses (e.g., porphyria, herbicide exposure) and the development of anticancer agents. Therefore, we prepared new potential inhibitors with Schiff base structural motifs (2-hydroxybenzaldehyde-based Schiff bases 9–13 and chromanone derivatives 17–19) as structurally relevant to PPO herbicides. The inhibitory activities (represented by the half maximal inhibitory concentration (IC50) values) and enzymatic interactions (represented by the hPPO melting temperatures) of these synthetic compounds and commercial PPO herbicides used against hPPO were studied by a protoporphyrin IX fluorescence assay. In the case of PPO herbicides, significant hPPO inhibition and changes in melting temperature were observed for oxyfluorten, oxadiazon, lactofen, butafenacil, saflufenacil, oxadiargyl, chlornitrofen, and especially fomesafen. Nevertheless, the prepared compounds did not display significant inhibitory activity or changes in the hPPO melting temperature. However, a designed model of hPPO inhibitors based on the determined IC50 values and a docking study (by using AutoDock) found important parts of the herbicide structural motif for hPPO inhibition. This model could be used to better predict PPO herbicidal toxicity and improve the design of synthetic inhibitors. Full article
(This article belongs to the Special Issue Advances in Anticancer Agents)
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12 pages, 5101 KiB  
Article
In Vitro Molecular Biology Studies of Spirooxindole Heterocyclic Hybrids
by Dhaifallah M. Al-thamili, Abdulrahman I. Almansour, Natarajan Arumugam, Faruq Mohammad and Raju Suresh Kumar
Processes 2020, 8(11), 1473; https://doi.org/10.3390/pr8111473 - 17 Nov 2020
Cited by 2 | Viewed by 1558
Abstract
 In the present report, we provide the results of the molecular biology studies of spiroheterocyclic hybrids, where the derivatives are found to possess potential anticancer activity towards cancer cells. A series of spiroxindole–pyrrolidine heterocyclic hybrids were evaluated for cell viability and proliferation [...] Read more.
 In the present report, we provide the results of the molecular biology studies of spiroheterocyclic hybrids, where the derivatives are found to possess potential anticancer activity towards cancer cells. A series of spiroxindole–pyrrolidine heterocyclic hybrids were evaluated for cell viability and proliferation against HepG2 cancer cells at concentrations in the range of 12.5–200 µg/mL over two different time periods of 24 and 48 h. In addition, the highly active compounds were also verified for their behavior towards noncancer cells (L929 cells), and it was found that the tested derivatives were not aggressive due to the observation of only limited cell loss, as compared to the cancer cells. Further analysis of the observed toxicity mechanism showed the apoptotic pathway was mediated by oxidative stress, with the involvement of caspases. Full article
(This article belongs to the Special Issue Advances in Anticancer Agents)
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15 pages, 4355 KiB  
Article
Functionalized N-Pyridinylmethyl Engrafted Bisarylmethylidenepyridinones as Anticancer Agents
by Dhaifallah M. Al-thamili, Abdulrahman I. Almansour, Natarajan Arumugam, Faruq Mohammad and Raju Suresh Kumar
Processes 2020, 8(9), 1154; https://doi.org/10.3390/pr8091154 - 15 Sep 2020
Cited by 5 | Viewed by 1806
Abstract
Structurally interesting N-pyridinylmethyl engrafted bisarylmethylidenepyridinones with high functionality have been constructed in good yield. The structural interpretation of these compounds has been done with the aid of spectroscopic analysis and further established by single crystal X-ray diffraction studies. Following physical characterization, the [...] Read more.
Structurally interesting N-pyridinylmethyl engrafted bisarylmethylidenepyridinones with high functionality have been constructed in good yield. The structural interpretation of these compounds has been done with the aid of spectroscopic analysis and further established by single crystal X-ray diffraction studies. Following physical characterization, the synthesized compounds were tested for their in vitro anticancer activity against HepG2 cancer cells and it was found that all of the compounds exhibited some level of activity. We observed a significant level of cell viability losses to the cancer cells, while only smaller losses to the non-cancer cells were observed. Besides, the mechanistic investigation of toxicology revealed that the cancer cells were undergoing apoptotic pathway, induced by the generation of oxidative stress and the involvement of caspases. The analysis provides preliminary evidence for the successful control of cancer cells with a minimal effect on healthy normal cells because of the high IC50 levels and cell death mechanisms. Full article
(This article belongs to the Special Issue Advances in Anticancer Agents)
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Review

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15 pages, 1687 KiB  
Review
Highly Specific L-Type Amino Acid Transporter 1 Inhibition by JPH203 as a Potential Pan-Cancer Treatment
by Arifudin Achmad, Shinta Lestari, Holis Abdul Holik, Driyanti Rahayu, Muhammad Hasan Bashari, Ahmad Faried and Achmad Hussein Sundawa Kartamihardja
Processes 2021, 9(7), 1170; https://doi.org/10.3390/pr9071170 - 5 Jul 2021
Cited by 10 | Viewed by 3316
Abstract
Accelerated cancer cell growth requires a massive intake of amino acids. Overexpression of L-type (large) amino acid transporter 1 (LAT1) on the cancer cell membrane facilitates such a demand, which is limited in normal organs. Therefore, LAT1 overexpression is ideal as a molecular [...] Read more.
Accelerated cancer cell growth requires a massive intake of amino acids. Overexpression of L-type (large) amino acid transporter 1 (LAT1) on the cancer cell membrane facilitates such a demand, which is limited in normal organs. Therefore, LAT1 overexpression is ideal as a molecular cancer therapeutic target. JPH203, a LAT1-selective non-transportable blocker, had demonstrated LAT1 inhibition in <10 µM IC50 values and effectively suppressed cancer cell growth in studies involving several types of cancer cell lines and tumor xenograft models. A limited phase I clinical trial was performed on five different solid tumors and showed that JPH203 is well-tolerated and has a promising activity for the treatment of bile duct cancer. This review details the development and prospect of JPH203 as a LAT1-targeting cancer therapy. Full article
(This article belongs to the Special Issue Advances in Anticancer Agents)
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17 pages, 1164 KiB  
Review
The Effects of Conjugated Linoleic Acids on Cancer
by Marko Dachev, Jana Bryndová, Milan Jakubek, Zdeněk Moučka and Marian Urban
Processes 2021, 9(3), 454; https://doi.org/10.3390/pr9030454 - 3 Mar 2021
Cited by 33 | Viewed by 7917
Abstract
Conjugated linoleic acids (CLA) are distinctive polyunsaturated fatty acids. They are present in food produced by ruminant animals and they are accumulated in seeds of certain plants. These naturally occurring substances have demonstrated to have anti-carcinogenic activity. Their potential effect to inhibit cancer [...] Read more.
Conjugated linoleic acids (CLA) are distinctive polyunsaturated fatty acids. They are present in food produced by ruminant animals and they are accumulated in seeds of certain plants. These naturally occurring substances have demonstrated to have anti-carcinogenic activity. Their potential effect to inhibit cancer has been shown in vivo and in vitro studies. In this review, we present the multiple effects of CLA isomers on cancer development such as anti-tumor efficiency, anti-mutagenic and anti-oxidant activity. Although the majority of the studies in vivo and in vitro summarized in this review have demonstrated beneficial effects of CLA on the proliferation and apoptosis of tumor cells, further experimental work is needed to estimate the true value of CLA as a real anti-cancer agent. Full article
(This article belongs to the Special Issue Advances in Anticancer Agents)
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10 pages, 1636 KiB  
Review
Evolution of Nitrogen-Based Alkylating Anticancer Agents
by Fredrik Lehmann and Johan Wennerberg
Processes 2021, 9(2), 377; https://doi.org/10.3390/pr9020377 - 19 Feb 2021
Cited by 34 | Viewed by 9030
Abstract
Despite the significant progress in anticancer drug development over recent years, there is a vital need for newer agents with unique, but still effective, mechanisms of action in order to treat the disease, particularly the highly aggressive and drug-resistant types. Alkylating agents, in [...] Read more.
Despite the significant progress in anticancer drug development over recent years, there is a vital need for newer agents with unique, but still effective, mechanisms of action in order to treat the disease, particularly the highly aggressive and drug-resistant types. Alkylating agents, in particular nitrogen-based alkylators, are commonly used to treat hematological and solid malignancies; they exert their antineoplastic effects at all phases of the cell cycle and prevent reproduction of tumor cells. Certain alkylating agents have been designed to be more lipophilic, enabling the compound to penetrate the cell and enhance its alkylating activity against tumors. This review details the evolution of currently available alkylating agents and their profiles, with a focus on nitrogen-based alkylating agents, as important anticancer therapy strategies. Full article
(This article belongs to the Special Issue Advances in Anticancer Agents)
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