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Pharmaceutics
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Advances in Anticancer Agent, 2nd Edition
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Advances in Anticancer Agent, 2nd Edition

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: closed (10 May 2025) | Viewed by 7805

Special Issue Editors

Dr. Noelia Duarte

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Guest Editor
iMed.ULisboa—Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Avenida Prof. Gama Pinto, 1649-019 Lisbon, Portugal
Interests: natural products; bioactive compounds; terpenes; phenolics; plant derived compounds; medicinal plants; natural products chemistry; mass spectrometry; multidrug resistance; medicinal chemistry
Special Issues, Collections and Topics in MDPI journals
Dr. Ana Paula Francisco

E-Mail Website
Guest Editor
Faculty of Pharmacy, University of Lisbon, Avenida Prof. Gama Pinto, 1649-019 Lisbon, Portugal
Interests: drug design; anticancer compounds; prodrug chemistry; drug delivery systems
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

According to the World Health Organization, cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2020. The cancer burden could be reduced by avoiding several risk factors, through appropriate screening and early detection and through the clinical treatment of neoplastic diseases. Chemotherapy remains a cornerstone among the several approaches to treatment, even though intrinsic or acquired resistance and metastasis remain major obstacles to a successful cure. In the last two decades, outstanding progress in genetics and molecular biology has prompted the discovery of novel molecular targets. Moreover, major advances in computational and in silico methods, combinatorial chemistry, chemical synthesis and natural products chemistry have provided new leads for the development of novel anticancer drugs. Nevertheless, and despite the vast number of compounds that have reached the stage of preclinical and clinical studies, the research and development of new anticancer agents and therapeutic strategies is a continuous process and constitutes the main subject of this Special Issue of Pharmaceutics. We welcome original or review articles concerning the discovery and development of new anticancer agents obtained from either synthesis or natural sources, and the submission of studies on topics such as drug targeting, drug design, pharmacokinetics, computer-aided drug design, in silico studies, drug repurposing, pharmacodynamics and drug delivery is greatly encouraged.

We look forward to receiving your contributions.

Dr. Noelia Duarte
Dr. Ana Paula Francisco
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. Pharmaceutics 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 2900 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

  • synthetic/natural anticancer agents
  • drug design
  • targeted therapies
  • hybrid compounds
  • metastasis
  • multidrug resistance

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Published Papers (4 papers)

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22 pages, 7452 KiB  
Article
Anti-Breast Cancer Properties and In Vivo Safety Profile of a Bis-Carbazole Derivative
by Jessica Ceramella, Camillo Rosano, Domenico Iacopetta, Iméne Ben Toumia, Leila Chekir-Ghedira, Mouna Maatouk, Annaluisa Mariconda, Pasquale Longo, Patrick Dallemagne, Christophe Rochais and Maria Stefania Sinicropi
Pharmaceutics 2025, 17(4), 415; https://doi.org/10.3390/pharmaceutics17040415 - 25 Mar 2025
Viewed by 399
Abstract
Background: Carbazoles represent one of the most important classes of nitrogen-based tricyclic aromatic heterocycles and are present in natural sources and chemically obtained drugs. Recently, several research groups disclosed their large biological and chemical applications in different fields, leading to an increased interest [...] Read more.
Background: Carbazoles represent one of the most important classes of nitrogen-based tricyclic aromatic heterocycles and are present in natural sources and chemically obtained drugs. Recently, several research groups disclosed their large biological and chemical applications in different fields, leading to an increased interest towards this class of molecules. Some of the obtained derivatives have been successfully employed in the clinical treatment of different tumor types, but the onset of heavy side effects impaired their efficacy and discouraged their use. Pursuing the aim of obtaining carbazoles with less negative features, a lot of chemically modified compounds have been produced and evaluated. Objectives/Methods: In this paper, we describe the in vitro and in vivo evaluation of a bis-carbazole derivative with strong anticancer properties against two breast cancer cell lines. Results: This compound has been found to impact the cell cytoskeleton dynamics, triggering the activation of some key proteins playing a role in the intrinsic and extrinsic apoptotic pathways. Equally important, this derivative has been found to be selective for cancer cells and has shown a safe profile in Balb/c-treated mice. Conclusions: Overall, the disclosed outcomes represent an important landmark for encouraging further studies directed toward the potentiation of this lead to be potentially exploited in both preclinical and clinical applications. Full article
(This article belongs to the Special Issue Advances in Anticancer Agent, 2nd Edition)
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20 pages, 2693 KiB  
Article
A Novel Class of Human ADAM8 Inhibitory Antibodies for Treatment of Triple-Negative Breast Cancer
by Nora D. Mineva, Stefania Pianetti, Sonia G. Das, Srimathi Srinivasan, Nicolas M. Billiald and Gail E. Sonenshein
Pharmaceutics 2024, 16(4), 536; https://doi.org/10.3390/pharmaceutics16040536 - 13 Apr 2024
Cited by 3 | Viewed by 2472
Abstract
New targeted treatments are urgently needed to improve triple-negative breast cancer (TNBC) patient survival. Previously, we identified the cell surface protein A Disintegrin And Metalloprotease 8 (ADAM8) as a driver of TNBC tumor growth and spread via its metalloproteinase and disintegrin (MP and [...] Read more.
New targeted treatments are urgently needed to improve triple-negative breast cancer (TNBC) patient survival. Previously, we identified the cell surface protein A Disintegrin And Metalloprotease 8 (ADAM8) as a driver of TNBC tumor growth and spread via its metalloproteinase and disintegrin (MP and DI) domains. In proof-of-concept studies, we demonstrated that a monoclonal antibody (mAb) that simultaneously inhibits both domains represents a promising therapeutic approach. Here, we screened a hybridoma library using a multistep selection strategy, including flow cytometry for Ab binding to native conformation protein and in vitro cell-based functional assays to isolate a novel panel of highly specific human ADAM8 dual MP and DI inhibitory mAbs, called ADPs. The screening of four top candidates for in vivo anti-cancer activity in an orthotopic MDA-MB-231 TNBC model of ADAM8-driven primary growth identified two lead mAbs, ADP2 and ADP13. Flow cytometry, hydrogen/deuterium exchange–mass spectrometry (HDX-MS) and alanine (ALA) scanning mutagenesis revealed that dual MP and DI inhibition was mediated via binding to the DI. Further testing in mice showed ADP2 and ADP13 reduce aggressive TNBC characteristics, including locoregional regrowth and metastasis, and improve survival, demonstrating strong therapeutic potential. The continued development of these mAbs into an ADAM8-targeted therapy could revolutionize TNBC treatment. Full article
(This article belongs to the Special Issue Advances in Anticancer Agent, 2nd Edition)
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18 pages, 1941 KiB  
Article
Acylation of Oleanolic Acid Oximes Effectively Improves Cytotoxic Activity in In Vitro Studies
by Barbara Bednarczyk-Cwynar and Piotr Ruszkowski
Pharmaceutics 2024, 16(1), 86; https://doi.org/10.3390/pharmaceutics16010086 - 9 Jan 2024
Cited by 3 | Viewed by 2086
Abstract
(1) Background: The aim of the presented work was to obtain a set of oleanolic acid derivatives with a high level of anticancer activity and a low level of toxicity by applying an economic method. Three types of oleanolic acid derivatives were obtained: [...] Read more.
(1) Background: The aim of the presented work was to obtain a set of oleanolic acid derivatives with a high level of anticancer activity and a low level of toxicity by applying an economic method. Three types of oleanolic acid derivatives were obtained: (i) derivatives of methyl oleanonate oxime, (ii) derivatives of methyl oleanonate oxime with an additional 11-oxo function, and (iii) derivatives of morpholide of oleanonic acid oxime. (2) Methods: The above oximes were acylated with aliphatic or aromatic carboxylic acid. The newly obtained compounds were subjected to ADMETox analysis and were also tested for cytotoxicity activity on the HeLa, KB, MCF-7, A-549, and HDF cell lines with the MTT assay. (3) Results: Among the tested acylated oximes of oleanolic acid, some derivatives, particularly those with two nitro groups attached to the aromatic ring, proved to be the most potent cytotoxic agents. These triterpene derivatives significantly inhibited the growth of the HeLa, KB, MCF-7, and A-549 cancer cell lines in micromolar concentrations. (4) Conclusions: The introduction of different moieties, particularly the 3,5-dinitro group, resulted in the synthesis of highly potent cytotoxic agents with favorable SI and ADMETox parameters. Full article
(This article belongs to the Special Issue Advances in Anticancer Agent, 2nd Edition)
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Review

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42 pages, 7869 KiB  
Review
Curcumin-Based Nanoparticles: Advancements and Challenges in Tumor Therapy
by Hicham Wahnou, Riad El Kebbaj, Bertrand Liagre, Vincent Sol, Youness Limami and Raphaël Emmanuel Duval
Pharmaceutics 2025, 17(1), 114; https://doi.org/10.3390/pharmaceutics17010114 - 15 Jan 2025
Cited by 5 | Viewed by 1933
Abstract
Curcumin, a bioactive compound derived from the rhizome of Curcuma longa L., has garnered significant attention for its potent anticancer properties. Despite its promising therapeutic potential, its poor bioavailability, rapid metabolism, and low water solubility hinder curcumin’s clinical application. Nanotechnology offers a viable [...] Read more.
Curcumin, a bioactive compound derived from the rhizome of Curcuma longa L., has garnered significant attention for its potent anticancer properties. Despite its promising therapeutic potential, its poor bioavailability, rapid metabolism, and low water solubility hinder curcumin’s clinical application. Nanotechnology offers a viable solution to these challenges by enabling the development of curcumin-based nanoparticles (CNPs) that enhance its bioavailability and therapeutic efficacy. This review provides a comprehensive overview of the recent advancements in the design and synthesis of CNPs for cancer therapy. We discuss various NP formulations, including polymeric, lipid-based, and inorganic nanoparticles, highlighting their role in improving curcumin’s pharmacokinetic and pharmacodynamic profiles. The mechanisms by which CNPs exert anticancer effects, such as inducing apoptosis, inhibiting cell proliferation, and modulating signaling pathways, are explored in details. Furthermore, we examine the preclinical and clinical studies that have demonstrated the efficacy of CNPs in treating different types of tumors, including breast, colorectal, and pancreatic cancers. Finally, the review addresses the current challenges and future perspectives in the clinical translation of CNPs, emphasizing the need for further research to optimize their design for targeted delivery and to enhance their therapeutic outcomes. By synthesizing the latest research, this review underscores the potential of CNPs as a promising avenue for advancing cancer therapy. Full article
(This article belongs to the Special Issue Advances in Anticancer Agent, 2nd Edition)
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