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: 31 October 2024 | Viewed by 1967

Special Issue Editors

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
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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

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Keywords

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

Published Papers (2 papers)

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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
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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 - 09 Jan 2024
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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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