The Promising Future of Anti-tumor Drugs

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 8236

Special Issue Editor

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
Interests: anticancer drug design and discovery

Special Issue Information

Dear Colleagues,

Cancer is a multifactorial disease with an extremely complex genesis and progression. The major challenge in the cancer therapy is the development of multidrug resistance and relapse. Conventional anticancer drugs directly target the DNA of the cell, while modern chemotherapeutic drugs include molecular-targeted therapy such as targeting the abnormal cell signaling inside the cancer cells. Targeted chemotherapy has been effective in several malignancies; however, the success has always been limited by drug resistance and/or side effects. Anticancer agents with multi-targeted action simultaneously modulate multiple cancer cell signaling pathways; therefore, they may ease the chance of effective anti-cancer drug development. To this end, there is an urgent need for the identification of predictive anticancer agents that may fight cancer with multi-targeted pathways, lower side effects, and/or have higher selectivity. We are pleased to invite you to contribute to our Special Issue entitled “The Promising Future of Anti-tumor Drugs”, which aims to collect contributions on the development of new anticancer agents. For this Special Issue, original research articles and reviews are welcome.

Research areas may include (but are not limited to) the following:

  • Design and synthesis of novel anticancer agents
  • Drug repurposing in the development of anticancer agents
  • Virtual screening of novel anticancer agents
  • Computer-aided drug design of novel anticancer agents
  • Anticancer drug discovery through plant extraction
  • Investigation on the pharmacological actions of anticancer drugs

We look forward to receiving your contributions.

Dr. Mohammed M. Alanazi
Guest Editor

Manuscript Submission Information

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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. Medicina 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 1800 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

  • anticancer drug discovery
  • anticancer drug design and synthesis
  • drug repurposing
  • computational methods in anticancer drug discovery
  • multi-targeted pathways
  • multi-kinase inhibitors

Published Papers (5 papers)

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Research

26 pages, 8019 KiB  
Article
Uridine Derivatives: Synthesis, Biological Evaluation, and In Silico Studies as Antimicrobial and Anticancer Agents
by Nasrin S. Munia, Mohammed M. Alanazi, Youness El Bakri, Ashwag S. Alanazi, Yousef E. Mukhrish, Imtiaj Hasan and Sarkar M. A. Kawsar
Medicina 2023, 59(6), 1107; https://doi.org/10.3390/medicina59061107 - 07 Jun 2023
Viewed by 1429
Abstract
Nucleoside analogs are frequently used in the control of viral infections and neoplastic diseases. However, relatively few studies have shown that nucleoside analogs have antibacterial and antifungal activities. In this study, a fused pyrimidine molecule, uridine, was modified with various aliphatic chains and [...] Read more.
Nucleoside analogs are frequently used in the control of viral infections and neoplastic diseases. However, relatively few studies have shown that nucleoside analogs have antibacterial and antifungal activities. In this study, a fused pyrimidine molecule, uridine, was modified with various aliphatic chains and aromatic groups to produce new derivatives as antimicrobial agents. All newly synthesized uridine derivatives were analyzed by spectral (NMR, FTIR, mass spectrometry), elemental, and physicochemical analyses. Prediction of activity spectra for substances (PASS) and in vitro biological evaluation against bacteria and fungi indicated promising antimicrobial capability of these uridine derivatives. The tested compounds were more effective against fungal phytopathogens than bacterial strains, as determined by their in vitro antimicrobial activity. Cytotoxicity testing indicated that the compounds were less toxic. In addition, antiproliferative activity against Ehrlich ascites carcinoma (EAC) cells was investigated, and compound 6 (2′,3′-di-O-cinnamoyl-5′-O-palmitoyluridine) demonstrated promising anticancer activity. Their molecular docking against Escherichia coli (1RXF) and Salmonella typhi (3000) revealed notable binding affinities and nonbonding interactions in support of this finding. Stable conformation and binding patterns/energy were found in a stimulating 400 ns molecular dynamics (MD) simulation. Structure–activity relationship (SAR) investigation indicated that acyl chains, CH3(CH2)10CO-, (C6H5)3C-, and C2H5C6H4CO-, combined with deoxyribose, were most effective against the tested bacterial and fungal pathogens. Pharmacokinetic predictions were examined to determine their ADMET characteristics, and the results in silico were intriguing. Finally, the synthesized uridine derivatives demonstrated increased medicinal activity and high potential for future antimicrobial/anticancer agent(s). Full article
(This article belongs to the Special Issue The Promising Future of Anti-tumor Drugs)
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16 pages, 1513 KiB  
Article
Design and Synthesis of New 4-(3,4,5-Trimethoxyphenyl)Thiazole–Pyrimidine Derivatives as Potential Antiproliferative Agents
by Ashraf K. El-Damasy, Heewon Jin, Mohamed A. Sabry, Hyun Ji Kim, Mohammed M. Alanazi, Seon Hee Seo, Eun-Kyoung Bang and Gyochang Keum
Medicina 2023, 59(6), 1076; https://doi.org/10.3390/medicina59061076 - 02 Jun 2023
Cited by 2 | Viewed by 1713
Abstract
A new series of 3,4,5-trimethoxyphenyl thiazole pyrimidines has been synthesized and biologically evaluated for its in vitro anticancer activity. Compounds 4a, 4b, and 4h with substituted piperazine showed the best antiproliferative activity. In the NCI-60 cell line screening, compound 4b showed [...] Read more.
A new series of 3,4,5-trimethoxyphenyl thiazole pyrimidines has been synthesized and biologically evaluated for its in vitro anticancer activity. Compounds 4a, 4b, and 4h with substituted piperazine showed the best antiproliferative activity. In the NCI-60 cell line screening, compound 4b showed promising cytostatic activity against multiple cell lines. Notably, it elicited a GI value of 86.28% against the NSCL cancer cell line HOP-92 at a 10 μM dose. Compounds 4a and 4h at 10 μM showed promising GI values of 40.87% and 46.14% against HCT-116 colorectal carcinoma and SK-BR-3 breast cancer cell lines, respectively. ADME-Tox prediction of compounds 4a, 4b, and 4h revealed their acceptable drug-likeness properties. In addition, compounds 4a, 4b, and 4h showed a high probability of targeting kinase receptors via Molinspiration and Swiss TargetPrediction. Full article
(This article belongs to the Special Issue The Promising Future of Anti-tumor Drugs)
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14 pages, 1859 KiB  
Article
Novel High-Throughput Microwell Spectrophotometric Assay for One-Step Determination of Lorlatinib, a Novel Potent Drug for the Treatment of Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small Cell Lung Cancer
by Abdullah M. Al-Hossaini, Ibrahim A. Darwish and Hany W. Darwish
Medicina 2023, 59(4), 756; https://doi.org/10.3390/medicina59040756 - 13 Apr 2023
Cited by 1 | Viewed by 1393
Abstract
Background and Objectives: Lorlatinib (LOR) belongs to the third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors. People who are diagnosed with ALK-positive metastatic and advanced non-small cell lung cancer (NSCLC) are eligible to get it as a first-line treatment option after it was [...] Read more.
Background and Objectives: Lorlatinib (LOR) belongs to the third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors. People who are diagnosed with ALK-positive metastatic and advanced non-small cell lung cancer (NSCLC) are eligible to get it as a first-line treatment option after it was given the approval by “the Food and Drug Administration (FDA)”. However, no study has described constructing high-throughput analytical methodology for LOR quantitation in dosage form. For the first time, this work details the construction of a high-throughput, innovative microwell spectrophotometric assay (MW-SPA) for single-step assessment of LOR in its tablet form, for use in pharmaceutical quality control. Materials and Methods: Assay depended on charge transfer complex (CTC) formation between LOR, as electron donor, with 2,3-dichloro-3,5-dicyano-1,4-benzoquinone (DDQ), as π-electron acceptor. Reaction conditions were adjusted, the CTC was characterized by ultraviolet (UV)-visible spectrophotometry and computational molecular modeling, and its electronic constants were determined. Site of interaction on LOR molecule was allocated and reaction mechanism was suggested. Under refined optimum reaction conditions, the procedures of MW-SPA were performed in 96-well assay plates, and the responses were recorded by an absorbance plate reader. Validation of the current methodology was performed in accordance with guidelines of “the International Council on Harmonization (ICH)”, and all validation parameters were acceptable. Results: Limits of detection and quantitation of MW-SPA were 1.8 and 5.5 µg/well, respectively. The assay was applied with great success for determining LOR in its tablets. Conclusions: This The assay is straightforward, economic and has high-throughput characteristics. Consequently, the assay is recommended as a valuable analytical approach in quality control laboratories for LOR’s tablets’ analysis. Full article
(This article belongs to the Special Issue The Promising Future of Anti-tumor Drugs)
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18 pages, 3310 KiB  
Article
Antiproliferative Activity, Multikinase Inhibition, Apoptosis- Inducing Effects and Molecular Docking of Novel Isatin–Purine Hybrids
by Ashwag S. Alanazi, Tebyan O. Mirgany, Aisha A. Alsfouk, Nawaf A. Alsaif and Mohammed M. Alanazi
Medicina 2023, 59(3), 610; https://doi.org/10.3390/medicina59030610 - 19 Mar 2023
Cited by 7 | Viewed by 1560
Abstract
The traditional single-treatment strategy for cancer is frequently unsuccessful due to the complexity of cellular signaling. However, suppression of multiple targets is vital to defeat tumor cells. In this research, new compounds for the treatment of cancer were developed successfully as novel hybrid [...] Read more.
The traditional single-treatment strategy for cancer is frequently unsuccessful due to the complexity of cellular signaling. However, suppression of multiple targets is vital to defeat tumor cells. In this research, new compounds for the treatment of cancer were developed successfully as novel hybrid anticancer agents. Based on a molecular hybridization strategy, we designed hybrid agents that target multiple protein kinases to fight cancer cells. The proposed hybrid agents combined purine and isatin moieties in their structures with 4-aminobenzohydrazide and hydrazine as different linkers. Having those two moieties in one molecule enabled the capability to inhibit multiple kinases, such as human epidermal receptor (EGFR), human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor receptor 2 (VEGFR2) and cyclin-dependent kinase 2 (CDK2). Anticancer activity was evaluated by performing cytotoxicity assays, kinase inhibition assays, cell cycle analysis, and BAX, Bcl-2, Caspase 3 and Caspase 9 protein level determination assays. The results showed that the designed hybrids tackled the cancer by inhibiting both cell proliferation and metastasis. A molecular docking study was performed to predict possible binding interactions in the active site of the investigated protein kinase enzymes. Full article
(This article belongs to the Special Issue The Promising Future of Anti-tumor Drugs)
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13 pages, 1246 KiB  
Article
Chemical Composition, Antibacterial Activity and In Vitro Anticancer Evaluation of Ochradenus baccatus Methanolic Extract
by Weam M. A. Khojali, Weiam Hussein, Mohammed Khaled Bin Break, Ahmed Alafnan, Bader Huwaimel, Nasrin E. Khalifa, Wafa F. S. Badulla, Raghad Abdulkarem Alshammari, Lama Khalid Alshammari, Rehab Aladham Raji Alshammari, Sara Mohsen Albarak, Enas Hmdan Alrkad, Tooba Mahboob and Hisham Alshammari
Medicina 2023, 59(3), 546; https://doi.org/10.3390/medicina59030546 - 10 Mar 2023
Viewed by 1561
Abstract
Background and Objectives: Ochradenus baccatus belongs to the family Resedaceae. It is widely spread in Saudi Arabia and other countries in Southwest Asia. O. baccatus is extensively used in traditional medicine as an anti-inflammatory and antibacterial agent, in addition to being a vital [...] Read more.
Background and Objectives: Ochradenus baccatus belongs to the family Resedaceae. It is widely spread in Saudi Arabia and other countries in Southwest Asia. O. baccatus is extensively used in traditional medicine as an anti-inflammatory and antibacterial agent, in addition to being a vital source of food for certain desert animal species. The aim of the present study was to investigate the chemical composition and antibacterial/anticancer activities of O. baccatus methanolic extracts collected from Hail, Saudi Arabia. Materials and Methods: The O. baccatus extracts were obtained by macerating the crude powder in methanol, followed by filtration and evaporation. Liquid chromatography–mass spectrometry (LC-MS) was used to analyze the methanolic extracts’ chemical constituents. Broth microdilution assay for minimum inhibitory concentration (MIC) determination was used to assess antimicrobial activity, while the extracts’ anticancer potential was assessed by sulforhodamine B Assay (SRB) assay. Results: The results of the antibacterial assay showed that the methanolic extracts from the roots and branches possessed varying degrees of activity against particular bacterial strains, with the highest activity being exerted by the branches’ extract against Escherichia coli and Salmonella typhimurium (St), demonstrating MIC values of 15.6 µg/mL and 20 µg/mL, respectively. Furthermore, the SRB cell viability assay revealed that only the branches’ extract inhibited the growth of A549 cancer cells, with an IC50 value of 86.19 µg/mL. The LC-MS analysis of the methanolic extracts from the plant’s roots and branches was then conducted, resulting in the identification of 8 and 13 major chemical constituents, respectively. Azelaic acid, β-amyrin, and phytanic acid are some of the bioactive compounds that were detected in the extracts via LC-MS, and they are thought to be responsible for the observed antibacterial/anticancer activity of O. baccatus methanolic extracts. Conclusions: This study confirmed the antibacterial/anticancer potential of O. baccatus methanolic extracts and analyzed their phytochemical constituents. Further isolation and biological screening are warranted to understand the therapeutic potential of O. baccatus. Full article
(This article belongs to the Special Issue The Promising Future of Anti-tumor Drugs)
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