Vol 24, No 7 (2024)
- Year: 2024
- Articles: 6
- URL: https://snv63.ru/1871-5206/issue/view/10001
Oncology
Potential of Nanomedicines as an Alternative for the Treatment of Colorectal Cancer - A Review
Abstract
:Colorectal cancer is the third most common cancer and the second in cases of cancer-related death. Polytherapy generates many adverse effects, leading the patient to give up. Nanotechnology has been studied in recent years to circumvent limitations. Groups composed of polymeric, lipid, and inorganic nanoparticles are the most purpose. Thus, the objective of this work is to bring information on how nanosystems can improve the chemotherapeutic treatment for colorectal cancer. Therefore, a search in journals such as \"LILACS\", \"SciELO\" and \"PubMed/Medline\" was performed, resulting in 25,000 articles found when applied the search engines \"nanoparticle,\" \"colorectal cancer,\" \"malignant neoplasms,\" and \"chemotherapy.\" After inclusion and exclusion factors, 24 articles remained, which were used as the basis for this integrative review. The results reveal that, regardless of the choice of matrix, nanoparticles showed an increase in bioavailability of the active, increasing the half-life by up to 13 times, modified release, as well as a significant reduction in tumor size, with cell viability up to 20% lower than the free drug tested, in different colorectal cancer cell lines, such as HCT-116, HT-29, and CaCo-2. However, more in vivo and clinical studies need to be performed, regardless of the formulation of its matrix, aiming at a higher rate of safety for patients and stability of the formulations, as well as knowledge of detailed indices of its pharmacokinetics and pharmacodynamics, seeking to avoid further damage to the recipient organism.
477-487
An Insight into the Effect of Schiff Base and their d and f Block Metal Complexes on Various Cancer Cell Lines as Anticancer Agents: A Review
Abstract
Over the last few decades, an alarming rise in the percentage of individuals with cancer and those with multi-resistant illnesses has forced researchers to explore possibilities for novel therapeutic approaches. Numerous medications currently exist to treat various disorders, and the development of small molecules as anticancer agents has considerable potential. However, the widespread prevalence of resistance to multiple drugs in cancer indicates that it is necessary to discover novel and promising compounds with ideal characteristics that could overcome the multidrug resistance issue. The utilisation of metallo-drugs has served as a productive anticancer chemotherapeutic method, and this approach may be implemented for combating multi-resistant tumours more successfully. Schiff bases have been receiving a lot of attention as a group of compounds due to their adaptable metal chelating abilities, innate biologic properties, and versatility to tweak the structure to optimise it for a specific biological purpose. The biological relevance of Schiff base and related complexes, notably their anticancer effects, has increased in their popularity as bio-inorganic chemistry has progressed. As a result of learning about Schiff bases antitumor efficacy against multiple cancer cell lines and their complexes, researchers are motivated to develop novel, side-effect-free anticancer treatments. According to study reports from the past ten years, we are still seeking a powerful anticancer contender. This study highlights the potential of Schiff bases, a broad class of chemical molecules, as potent anticancer agents. In combination with other anticancer strategies, they enhance the efficacy of treatment by elevating the cytotoxicity of chemotherapy, surmounting drug resistance, and promoting targeted therapy. Schiff bases also cause cancer cell DNA repair, improve immunotherapy, prevent angiogenesis, cause apoptosis, and lessen the side effects of chemotherapy. The present review explores the development of potential Schiff base and their d and f block metal complexes as anticancer agents against various cancer cell lines.
488-503
Design, Synthesis, In vitro and In vivo Evaluation of New Imidazo[1,2-a]pyridine Derivatives as Cyclooxygenase-2 Inhibitors
Abstract
Background:Cyclooxygenase-2 (COX-2), the key enzyme in the arachidonic acid conversion to prostaglandins, is one of the enzymes associated with different pathophysiological conditions, such as inflammation, cancers, Alzheimer's, and Parkinson's disease. Therefore, COX-2 inhibitors have emerged as potential therapeutic agents in these diseases.
Objectives:The objective of this study was to design and synthesize novel imidazo[1,2-a]pyridine derivatives utilizing rational design methods with the specific aim of developing new potent COX-2 inhibitors. Additionally, we sought to investigate the biological activities of these compounds, focusing on their COX-2 inhibitory effects, analgesic activity, and antiplatelet potential. We aimed to contribute to the development of selective COX-2 inhibitors with enhanced therapeutic benefits.
Methods:Docking investigations were carried out using AutoDock Vina software to analyze the interaction of designed compounds. A total of 15 synthesized derivatives were obtained through a series of five reaction steps. The COX-2 inhibitory activities were assessed using the fluorescent Cayman kit, while analgesic effects were determined through writing tests, and Born's method was employed to evaluate antiplatelet activities.
Results:The findings indicated that the majority of the tested compounds exhibited significant and specific inhibitory effects on COX-2, with a selectivity index ranging from 51.3 to 897.1 and IC50 values of 0.13 to 0.05 µM. Among the studied compounds, derivatives 5e, 5f, and 5j demonstrated the highest potency with IC50 value of 0.05 µM, while compound 5i exhibited the highest selectivity with a selectivity index of 897.19. In vivo analgesic activity of the most potent COX-2 inhibitors revealed that 3-(4-chlorophenoxy)-2-[4-(methylsulfonyl) phenyl] imidazo[1,2-a]pyridine (5j) possessed the most notable analgesic activity with ED50 value of 12.38 mg/kg. Moreover, evaluating the antiplatelet activity showed compound 5a as the most potent for inhibiting arachidonic acidinduced platelet aggregation. In molecular modeling studies, methylsulfonyl pharmacophore was found to be inserted in the secondary pocket of the COX-2 active site, where it formed hydrogen bonds with Arg-513 and His-90.
Conclusion:The majority of the compounds examined demonstrated selectivity and potency as inhibitors of COX-2. Furthermore, the analgesic effects observed of potent compounds can be attributed to the inhibition of the cyclooxygenase enzyme.
504-513
Novel N-(3-ethynyl Phenyl)-6,7-bis(2-methoxyethoxy)Quinazoline-4-amine Derivatives: Synthesis, Characterization, Anti-cancer Activity, In-silico and DFT Studies
Abstract
Background:Cancer is one of the most common reasons for mortality in the world. A continuous effort to develop effective anti-cancer drugs with minimum side effects has become necessary. The use of small-molecule drugs has revolutionized cancer research by inhibiting cancer cell survival and proliferation. Quinazolines are a class of bioactive heterocyclic compounds with active pharmacophores in several anti-cancer drugs. Such small molecule inhibitors obstruct the significant signals responsible for cancer cell development, thus blocking these cell signals to prevent cancer development and spread.
Objective:In the current study, novel quinazoline derivatives structurally similar to erlotinib were synthesized and explored as novel anti-cancer agents.
Methods:All the synthesized molecules were confirmed by spectroscopic techniques like 1H NMR, 13C NMR, and ESI-MS. Various techniques were applied to study the protein-drug interaction, DFT analysis, Hirshfeld surface, and target prediction. The molecules were screened in vitro for their anti-cancer properties against 60 human tumor cell lines. The growth inhibitory properties of a few compounds were studied against the MCF7 breast cancer cell line.
Results:The activity of compounds 9f, 9o, and 9s were found to be active. However, compound 9f is more active when compared with other compounds.
Conclusion:Some synthesized compounds were active against different cancer cell lines. The in-vitro study results were found to be in agreement with the predictions from in-silico data. The selected molecules were further subjected to get the possible mechanism of action against different cancer cells.
514-532
Preparation, Characterization, and Anticancer Activity Assessment of Chitosan/TPP Nanoparticles Loaded with Echis carinatus Venom
Abstract
Aims and Background:Echis carinatus venom is a toxic substance naturally produced by special glands in this snake species. Alongside various toxic properties, this venom has been used for its therapeutic effects, which are applicable in treating various cancers (liver, breast, etc.).
Objective:Nanotechnology-based drug delivery systems are suitable for protecting Echis carinatus venom against destruction and unwanted absorption. They can manage its controlled transfer and absorption, significantly reducing side effects
Methods:In the present study, chitosan nanoparticles were prepared using the ionotropic gelation method with emulsion cross-linking. The venom's encapsulation efficiency, loading capacity, and release rate were calculated at certain time points. Moreover, the nanoparticles' optimal formulation and cytotoxic effects were determined using the MTT assay.
Results:The optimized nanoparticle formulation increases cell death induction in various cancerous cell lines. Moreover, chitosan nanoparticles loaded with Echis carinatus venom had a significant rate of cytotoxicity against cancer cells.
Conclusion:It is proposed that this formulation may act as a suitable candidate for more extensive assessments of cancer treatment using nanotechnology-based drug delivery systems.
533-543
Design and Synthesis of Aspirin-chalcone Mimic Conjugates as Potential Anticancer Agents
Abstract
Background:Extensive research has been conducted on aspirin, a widely recognized NSAID medication, regarding its potential as an anticancer agent. Studies have revealed its ability to trigger cell death in different types of cancer cells.
Methods:A set of aspirin-chalcone mimic conjugates 5a-k and 6a-d utilizing the freshly prepared acid chloride of aspirin moiety has been designed and synthesized. To evaluate the newly developed compounds, the NCI 60- cell line panel was employed to assess their anti-proliferative properties. Subsequently, cell cycle analysis was conducted along with an examination of the compounds' impact on the levels of p53, Bax, Bcl-2, active caspase- 3, and their inhibition mechanism of tubulin polymerization.
Results:Derivative 6c displayed the best anticancer activity among the tested series while 6d was the best against breast cancer MDA-MB-468, therefore both of them were selected for the 5-dose stage, however, targeting MDA-MB-468, PI-flow cytometry of compound 6d proved the triggered cell growth arrest at the G1/S phase avoiding the mitotic cycle in MDA-MB-468 cells. Similarly, the upregulation of oncogenic parameters such as caspase-3, p53, and Bax/Bcl-2, along with the inhibition of PARP-1 enzyme level, was observed with compound 6d. This compound also exhibited a significant ability to induce apoptosis and disrupt the intracellular microtubule network through a promising activity as a tubulin polymerization inhibitor with IC50 = 1.065 ± 0.024 ng/ml. Furthermore, to examine the manner in which compound 6d binds to the active pocket of the tubulin polymerization enzyme, a molecular docking study was conducted.
Conclusion:The study indicated that compound 6d could be a powerful microtubule-destabilizing agent. Therefore, further research on 6d could be worthwhile.
544-557