Page 129 - EJMO-9-2

Eurasian Journal of Medicine and
Oncology
Anticancer effects of phytocomposites

tumorigenesis. RAS mutations are found in approximately FDA in 2011 and 2004, respectively. Moreover, several
30% of all human tumors. Specifically, Kirsten RAS drugs like TAK-659, DZD9008, AZD5991, SHR- 3162,
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(KRAS) mutations are prevalent in lung cancer (32%), resveratrol, quercetin, and epigallocatechin gallate are
colorectal cancer (40%), and pancreatic cancer (85 – currently undergoing clinical trials. 29-35 These examples
90%). 13-15 While HRAS mutations are less common than highlight the importance of computational methods in
KRAS and neuroblastoma RAS (NRAS) mutations, they are designing anticancer drugs, paving the way for novel
the most frequently detected in head and neck cancers. 16,17 drug discoveries that can improve patient’s quality of life.
In this study, molecular docking was used to analyze the
Anticancer drug discovery is a complex, time-
consuming, and expensive process that involves several binding affinities, total polar surface area (TPSA) values,
log P value, and bioavailability of the selected compounds
stages, including target identification, chemical synthesis, (tecomaquinone I, brevilin A, erybraedin A, evodiamine,
preclinical testing using in vitro and animal models, and sumadain C) with the target protein HRAS, which
and toxicity assessment. Successful compounds are then plays a role in cell proliferation and apoptosis. HRAS is
evaluated in clinical trials to assess their safety and efficacy a key oncogene involved in tumorigenesis, making it an
in the target patient population, which can take several important target for anticancer therapies. This study aimed
years to complete. Recent advancements in technology to assess the anticancer effects of these phytocompounds
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have led to the development of computer-aided drug in OSCC using in silico analysis like molecular docking.
designing (CADD). CADD is an efficient way to identify If the results are promising, further experimental and
potential compounds and aids in new drug development.
CADD encompasses various methods, including structure- clinical studies could lead to the development of effective
chemotherapeutic drugs.
based drug designing (molecular docking and molecular
dynamics) and ligand-based drug designing, such as ligand- 2. Methods
based pharmacophore modeling, quantitative structure-
activity relationship modeling, fragment-based drug Five phytocompounds with potential anticancer activity
designing, pharmacokinetics, and pharmacodynamics were selected through an extensive literature search.
modeling. These computational techniques simulate and These phytocompounds are: (i) Tecomaquinone I, a
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predict the interaction of drug molecules with their target quinone found in plants like Tectona grandis and Lippia
using computer algorithms on chemical and biological origanoides, with a molecular formula of C H O , (ii)
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4
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data. Several United States Food and Drug Administration brevilin A, a natural sesquiterpene lactone found in
(FDA)-approved anticancer drugs have been developed Centipeda minima, with a molecular formula of C H O ,
5
6
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using CADD. For example, crizotinib, which targets (iii) erybraedin A, a flavonoid from the Erythrina species,
hepatocyte growth factor receptors, anaplastic lymphoma with a molecular formula of C H O ,(iv) evodiamine, an
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4
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kinase, and tyrosine kinase mesenchymal-epithelial alkaloid from the dry unripened fruit of Evodiae fructus,
transition, was approved in 2011 for treating lymphoma, with a molecular formula C H N O, and (v) sumadain C,
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3
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esophageal cancer, and lung cancer. Axitinib, a vascular a monoterpene-chalcone conjugate found in the seeds of
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endothelial growth factor receptor inhibitor for advanced Alpinia katsumadai, with a molecular formula of C H O .
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5
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renal cell carcinoma, was approved in 2012. Recently, The simplified molecular input line entry system
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tubulin inhibitors have been developed using the ligand- (SMILES) notation for each compound is provided in
based technique that targets tubulin polymerization, a Table 1. The SMILES form is a notation system used
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vital process for cell cycle progression and division. In to represent the chemical structure of a drug in a linear
addition, a human aromatase inhibitor has been developed format. The chemical structures of the compounds were
through ligand-based approaches for the treatment of retrieved from the PubChem database in.sdf format and
estrogen receptor-positive breast cancer. Gefitinib, an converted into three-dimensional (3D) structures in.pdb
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EGFR inhibitor identified through structure-based design, format using the Open Babel software. The chemical
was approved by the FDA in 2015 to treat advanced or structures of the selected phytocompounds are given in
metastatic non-small cell lung cancer (NSCLC). Erlotinib, Figure 1. The 3D structure of the human HRAS protein
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approved in 2004, targets EGFR kinases and is used for was retrieved from the RCSB Protein Data Bank and is
treating pancreatic cancer and NSCLC, while lapatinib, shown in Figure 2. The SMILES form and the structures
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approved in 2007, targets ERBB2/EGFR to treat breast of the selected phytocompounds were obtained from
cancer. Other drugs, such as abiraterone, an androgen ZINC15, and a pharmacophore model was obtained
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synthesis inhibitor used for metastatic castration-resistant from ZINCPharmer. A combination of approximately 20
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prostate cancer, and imatinib, a tyrosine kinase inhibitor phytocomposites was selected based on their log P values,
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used for chronic myeloid leukemia, were approved by the TPSA values, and adherence to drug-likeliness rules
Volume 9 Issue 2 (2025) 121 doi: 10.36922/ejmo.7073