Letters in Drug Design & Discovery - Volume 20, Issue 8, 2023

Cancer-Associated Fibroblasts (CAFs) originate from the activation of fibroblasts in the Tumor Microenvironment (TME) during tumorigenesis, resulting in the promotion of tumor growth, metabolism, and metastasis. Exosomes, which can locally or remotely transfer miRNAs, lncRNAs, proteins, metabolites, and other substances to other cells, have a size and range distribution of 30 to 150 nm and have been described as new particles that mediate communication among neighboring and/or distant cells. Exosomes have regulatory roles in the tumor microenvironment that are different from those in the tumor cells, including mediating the regulation of tumor progression, delivery of miRNAs involved in reprogramming Normal Fibroblasts (NFs) into CAFs, and the modulation of tumor initiation and metastasis. Exosomes can be useful biomarkers of the tumor microenvironment and for the therapy and diagnosis of different diseases. Relevant interactions with cancer cells reprogram NFs into CAFs or allow cell-to-cell communication between CAFs and cancer cells. Several researchers have started exploring the precise molecular mechanisms related to exosome secretion, uptake, composition, and corresponding functions of their "cargo." However, little is known about the processes by which exosomes affect cancer behavior and their potential use as diagnostic biomarkers for cancer treatment. Therefore, the crosstalk between CAFs and exosomes during tumorigenesis and the effects of exosomes as biomarkers and drug carriers for therapy are discussed in this review.

KRAS is a highly mutated gene among cancers, especially in the lung, pancreatic and colorectal cancers (CRC). Despite extensive efforts in the past three decades, KRAS remains undruggable. But lately, inhibitors selectively binding to cysteine mutant at 12^thposition (G12C) are in clinical trials as a single agent and in combination with other drugs. FDA approved LUMAKRAS (Sotorasib, AMG510) for metastatic NSCLC, while Adagrasib (MRTX849) is under clinical trials, and it is showing good safety and efficacy in pancreatic and GI tumors. Both these molecules demonstrated better response in NSCLC but have less efficacy in colorectal and other solid cancers. Among non-G12C KRAS mutant cancers, promising data are emerging from G12D inhibition. This review covers the status of KRAS G12C, non- G12C inhibitors, and discusses different nodal proteins in the RAS signaling pathway, mechanism of resistance in targeted therapy and combination approaches. Ongoing clinical trials with G12C inhibitors have promising results. However, a combination of KRAS inhibition with other inhibitors of signaling components in vertical axis (SHP2, SOS1, MEK, PI3K/AKT and EGFR inhibitors) might be beneficial for durable clinical response. Sotorasib in combination with MEK inhibitor showed promising results in preclinical xenograft and PDx models of KRAS mutated cancers. Although at a preclinical stage, other approaches like Tri complex inhibitor, KRAS (ON) inhibitors, and non-G12C inhibitors are of significant interest in KRAS drug discovery. Multiple targeted approaches are being explored based on tumor specific gene expression profiles considering dynamic nature of KRAS activity and heterogeneity of hard to treat tumors.

Background: Epilepsy is one of the most common neurological disorders. Many individuals continue to have seizures despite medical and surgical treatments, suggesting that the discovery of novel anti-seizure drugs is vital. Triazole compounds are widely used as pharmaceuticals and have gained significant interest in medicinal chemistry. In this article, the development of triazoles, especially 1,2,4- triazole, in the field of anti-seizure therapeutics is reviewed. Methods: The relevant literature was investigated, classified, and analysed. This article attempts to systematically review the research of triazole derivatives in the design and development of anti-seizure agents during the past two decades through extensive literature research, which was based on the information accessible in PubMed, Science Direct, Google Scholar and other databases. Results: Research results demonstrate that triazoles occupy a distinct niche in heterocyclic chemistry and represent a key motif in medicinal chemistry because of their ability to exhibit an array of properties and bioactivities. Therefore, 1,2,4-triazole appears to be an important pharmacophore, especially in the field of anti-seizure therapeutics, where its promising potential value has been explored. Conclusion: This review presents a summary of the research related to 1,2,4-triazole, which acts as a potential anti-seizure pharmacophore that could be further developed. Compounds with 1,2,4-triazole or related structures had previously shown reasonable anti-seizure activity and safety. After thorough research of this structure, it is believed that 1,2,4-triazole-containing compounds will be further developed as anti-seizure drugs for clinical use.

Herbal medicine and phytochemicals have always been great therapeutic options to treat various diseases due to their compatibility, safety, easy production, low cost and side effects. However, low absorption rate, and poor bioavailability are notable challenges that have limited the use of most phytoconstituents. To address these challenges, different drug delivery methods have been proposed for generating operative carrier systems for phytochemicals. Among them, transdermal drug delivery (TDD) using nanophytosome has been introduced as a promising candidate for the delivery of insoluble phytoconstituents. Phytosomes can overcome skin barriers, and are therefore effective carriers for herbal medicines. They are generally produced by combining phytoconstituent agents in medicinal plant extracts with phospholipid molecules. They have improved the clinical applications of phytoconstituents such as polyphenols by enhancing their bioavailability and uptake. In this review, the main benefits of transdermal delivery systems, advantages of nanophytosome over other lipid nanoparticles in TDD of phytochemicals, and methods of phytosome preparation and characterization are briefly reviewed.

Introduction: N-methyl-d-aspartate receptor (NMDAR) and tau protein play an important role in neuronal death due to cerebral ischemia or ischemic stroke. Unfortunately, no drug has been discovered except tissue plasminogen activator (tPA) to fight against ischemic stroke. Virtual high throughput screening to find out possibilities of bioactive molecules to target NMDAR and tau protein to treat ischemic stroke may be an option for drug discovery. Objective: The current study aimed to assess the molecular interaction of some bioactive molecules with NMDAR and tau protein in silico to incriminate ischemic stroke. Methods: A computational method based on ligand-protein interaction technique has been used in the present study to identify the therapeutic potential of some bioactive molecules for the possible treatment of ischemic stroke. For this purpose, 50 bioactive molecules were screened and docking analysis was performed for two target proteins, NMDAR and tau protein. In this study, for each protein target, the best poses were identified based on binding energy and inhibition constant. Different pharmacological properties of selected bioactive molecules were also analyzed to determine their absorption, distribution, metabolism, excretion and toxicity (ADME/T) properties in silico. All were found in the acceptable range and followed Lipinski’s rule. Results: In the present study of the 50 screened bioactive molecules, top 10 molecules have been identified, of which best two bioactive molecules such as gossypin, viniferin have been predicted to be potential neuroprotective agents against cerebral ischemia induced alteration of NMDAR and tau protein functional integrities. Conclusion: Gossypin’ was the best bioactive compound interacting with NMDAR and tau protein.

Background: Tetrapyrrolic compounds, such as porphyrins and metalloporphyrins, are highly interesting for pharmaceutical chemistry designs considering their good biocompatibility and therapeutic potential. Objective: The aim of the present work was a preliminary in vitro evaluation of some unsymmetrical porphyrins and the corresponding symmetrical structures as potential candidates for the photodynamic therapy of malignant tumors. Methods: The biocompatibility of compounds was assessed in terms of their in vitro effect on the viability and proliferation of breast human carcinoma MCF-7 cells and human normal peripheral blood mononuclear cells. Results: Results indicated that unsymmetrical and symmetrical porphyrins were non-toxic against tumor MCF-7 cells in the concentration range of 0.2–2μM, making them valuable candidates for further development as photosensitizers for PDT in tumors. Moreover, unsymmetrical compounds tended to restore the response of normal and tumor cells affected by the vehicle (dimethyl sulfoxide) used for the initial solubilization of porphyrins, while the symmetrical compounds were less active in this respect. Conclusion: Unsymmetrical A3B type porphyrins prove enhanced capacity as potential theranostic agents in interaction with human carcinoma MCF-7 cells, despite reduced differences with the corresponding symmetrical form.

Background: In the diabetic condition, damage to the Müller cells contributes to the pathogenesis of diabetic retinopathy. Aims: This study aimed to investigate the protective effect of Bushen Huoxue, Traditional Chinese Medicine (BHTCM), on Müller in diabetic retinopathological conditions. Methods: Primary rat retinal Müller cells (RRMC) were isolated and cultured under high glucose (50 nmol/L). The advanced glycation end products (AGEs) and sodium dithionite were applied to treat highglucose administrated RRMC to mimic diabetic retinopathological conditions. The effects of BHTCM on diabetic retinopathological RRMC were evaluated. The expressions of aquaporin-4 (AQP4) and Kir4.1 were determined by double-labeling immunofluorescence and ELISA. Levels of vascular endothelial growth factor (VEGF), interleukin-1β (IL-1β) and pigment epithelium-derived factor (PEDF) were examined with ELISA. Lactate dehydrogenase (LDH) activity was also evaluated. Results: Retinal Müller cells were successfully isolated and identified. RRMC treated with AGEs and sodium dithionite resulted in the increase of AQP4 and decrease of Kir4.1 in RRMC, increase of VEGF and IL-1β secretion, increase of LDH activity, decrease of PEDF secretion in culture medium, all of which, in a dose-dependent or time-dependent manner. Post treating RRMC with AGEs and dithionite, BHTCM reversed changes in expression of AQP4 and Kir4.1 in RRMC, and reversed VEGF levels, PEDF and IL-1β secretion in the culture medium. Moreover, BHTCM reversed the decrease of RRMC cell membrane integrity after AGEs and dithionite treatment. Conclusion: BHTCM protected Müller cells from diabetic damage by reducing abnormal changes of Kir4.1 and AQP4, inhibiting VEGF and IL-1β, increasing PEDF production, and maintaining cell membrane integrity. Therefore, BHTCM is a potential drug for the treatment of diabetic retinopathy, which can correct the function of Müller cells.

Introduction: Although, several vaccines are being approved, no effective antiviral drug has been developed for COVID-19 infectious. The present investigation was aimed to increase the essential oils of Cuscuta campestris using far-red light treatment and examine the potential of crude extracts of C. campestris against selected pneumonia pathogens and COVID-19. Methods: Anti-COVID-19 activity was determined in human lung cell lines and COVID-19 positive patients. Results: Results demonstrated that the aqueous extract had the highest amount of anti-COVID-19, antibiotic and antioxidant activity. The far-red light treatment increased Scoparone, cineole, Benzofuran, 2, 3- dihydro, Cinnamic acid, and Benzo[h]quinoline, 2, 4-dimethyl, which are mainly effective components against COVID-19 inflammation and pneumonia microbes. CT scan and clinical laboratory tests in a clinical case study, a 30-year-old woman who presented with severe 2019-nCoV, demonstrated that inhalation of 30 mg extract nebulized/day for seven days resulted in significant improvement in consolidation and ground-glass opacity in lungs on the seventh day of treatment. Conclusion: It is hoped that this study leads to the introduction of some compounds that could be used to formulate new and more potent anti-COVID-19 antibiotics, or other drugs of natural origin in medicine.

Aim: The present work has been designed to discover some novel 2-substituted -5-hydroxy-1- (1-methyl-3-morpholinopropyl)-1H-indole-3-carboxamide derivatives and their screening through computational molecular docking. Background: The present manuscript describes designing novel 2-substituted-5-hydroxy-1-(1-methyl-3- morpholinopropyl)-1H-indole-3-carboxamide derivatives as specific ERα modulators, discusses the selection criteria for 1ERR, several interactions between the ligand and the amino acid residues that would probably elicit fruitful modulation of the receptor. Accordingly, a ligand was observed to yield a G Score of -10. 390, which was considered close and comparable with the standard ligand Raloxifene (-11.869). Objective: Synthesize a few indole -3-carboxamide derivatives and test their ability to modulate ER-α through human cell line cultures for breast cancer. The present manuscript describes the designing of novel 2-substituted -5-hydroxy-1-(1-methyl-3-morpholinopropyl)-1H-indole-3-carboxamide derivatives as specific ERα modulators, discusses the selection criteria for 1ERR, several interactions between the ligand and the amino acid residues that would probably elicit fruitful modulation of the ER-alpha in the treatment of breast cancer. Methods: This work involved designing a few 2-substituted-5-hydroxy-1-(1-methyl-3- morpholinopropyl)-1H-indole-3-carboxamide derivatives and their virtual screening for receptor modulation by carrying molecular docking studies to determine the binding interactions for best-fit conformations in AF-2 binding site of the ERα receptor, and ADME predictions by Quick Prop Tools. Those ligands that displayed satisfactory docking were selected for further studies. These revealed all-important functional groups that interact with active amino acid residues in the targeted cavity, substantiating their presence in molecules to elicit the desired response whence tested in vitro. Results: Based on the docking studies of the designed derivatives, ligands BD59, BD60, BD65, BD58, BD64 BD61, BD54, BD32, BD48 and BD45 have shown better binding energy than the rest and were comparable with the interactions shown by the standard, Raloxifene. The observed results lamented the presence of a substitution at the C-2 position of indole scaffold, either straight or branched with terminal atom containing non-bonding electrons (halo/-NH2). Accordingly, ligand BD59 carrying chlorobenzene chain (G Score= -10.390), whereas BD60 carrying flurobenzene chain (G Score = -10.204), whereas BD65 carrying methylbenzene chain (G Score = -9.863) were found to interact suitably with the active amino acid residues in the targeted cavity that are reported to be involved in interaction with the standard. Conclusion: From the present results, we conclude that designed derivatives have the potential to modulate ERα receptors effectively, which can be synthesized and tested for their effectiveness, in vitro and in vivo against breast cancer.

Background: Staphylococcus aureus (S. aureus) is a Gram-positive bacterium causing a wide range of human infections, leading to life-threatening invasive disorders, hospitalization, and mortality. Producing β-lactamase enzymes in S. aureus is one of the main mechanisms of the pathogen that makes the bacteria resistant to beta-lactam antibiotics, resulting in methicillin-resistant S. aureus (MRSA) strains. Therefore, it is crucial to identify novel β-lactamase inhibitors to combat infections caused by MRSA strains. Methods: In silico virtual screening approach was executed to evaluate the binding affinity of several natural flavonoids to the MRSA β-lactamase active site. After that, the stability of interactions between top inhibitors and the residues incorporated inside the β-lactamase was examined by molecular dynamics (MD) simulation. Moreover, the most connected amino acid within the catalytic domain of the enzyme was determined. Results: Rutin, isoquercitrin, nicotiflorin, quercetin-3-rhamnoside, vicenin-2, quercitrin, and orientin demonstrated a salient binding affinity with the β-lactamase active site (ΔG binding < −10 kcal/mol). Interestingly, the inhibition constant value (Ki) for rutin was estimated at the picomolar scale. The docked poses of these compounds were demonstrated to be stable. Moreover, Gln237 was revealed to be the most crucial residue involved in ligand binding. Conclusion: Rutin, isoquercitrin, nicotiflorin, quercetin-3-rhamnoside, vicenin-2, quercitrin, and orientin may be potent inhibitors of β-lactamase and may be helpful for the treatment of several invasive infections caused by MRSA strains. However, experimental studies are needed in the future to validate our findings.

Introduction: 2-Amino-7-hydroxy-4-phenyl-4H-chromene-3-carbonitrile (4) was synthesized through a three-component reaction in ethanol/piperidine solution. Methods: Synthesis of several new 4H-chromenes (5-14) has been achieved involving various reactions. The structure of these new compounds was confirmed using IR, ¹H NMR and ¹³C NMR, as well as MS spectroscopy. Results and Conclusion: All newly substituted chromene derivatives displayed potential analgesic and anticonvulsant activities. The structure-activity relationship study revealed that 2-amino-4-phenyl-3-(1Htetrazol- 5-yl)-4H-chromen-7-ol (13) was more beneficial than 8-hydroxy-2-methyl-5-phenyl-3,5-dihydro- 4H-chromeno[2,3-d]pyrimidin-4-one (11), 8-hydroxy-2,5-diphenyl-3,5-dihydro-4H-chromeno[2,3-d]pyrimidin- 4-one (12), and 8-hydroxy-5-phenyl-3,5-dihydro-4H-chromeno[2,3-d]pyrimidin-4-one (14) in terms of analgesic and anti-inflammatory activities.

Background: Anticipating the correlation between SARS-CoV-2 infection and ‘triplenegative breast cancer (TNBC)’ remains challenging. It has been reported that people currently diagnosed with cancer have a higher risk of severe complications if they are affected by the viral infection. Cancer treatments, including chemotherapy, targeted therapies, and immunotherapy, may weaken the immune system and possibly cause critical lung damage and breathing problems. Special attention must be paid to the ‘comorbidity condition’ while estimating the risk of severe SARSCoV- 2 infection in TNBC patients. Hence the work aims to study the correlation between triplenegative breast cancer (TNBC) and SARS-CoV-2 using biomolecular networking. Methods: The genes associated with SARS CoV-2 have been collected from curated data in Bio- GRID. TNBC-related genes have been collected from expression profiles. Molecular networking has generated a Protein-Protein Interaction (PPI) network and a Protein-Drug Interaction (PDI) network. The network results were further evaluated through molecular docking studies followed by molecular dynamic simulation. Results: The genetic correlation of TNBC and SARS-Cov-2 has been observed from the combined PPI of their proteins. The drugs interacting with the disease's closely associated genes have been identified. The docking and simulation study showed that anti-TNBC and anti-viral drugs interact with these associated targets, suggesting their influence in inhibiting both the disease mutations. Conclusion: The study suggests a slight influence of SARS-CoV-2 viral infection on Triple Negative Breast Cancer. Few anticancer drugs such as Lapatinib, Docetaxel and Paclitaxel are found to inhibit both TNBC and viral mutations. The computational studies suggest these molecules are also useful for TNBC patients to control SARS-CoV-2 infection.

Objectives: Glutamatergic dysfunction has been implicated in the pathogenesis of numerous central nervous system disorders. Artemisia absinthium (A. absinthium), has been reported to have neuroprotective and antioxidant activities. The current study examined the effect of A. absinthium extract on glutamate-induced cytotoxicity using PC12 cells. Methods: PC12 cells were pretreated with A. absinthium extract (70% ethanol) at concentration ranges of 6.25-25 μg/ml for 2 h, followed by exposure to glutamate (8 mM) for 24 hr. The cells viability, reactive oxygen species (ROS) accumulation, and lipid peroxidation were measured. Moreover, a propidium iodide flow cytometry assay was performed for the assessment of apoptosis. Results: Pretreatment with A. absinthium extract markedly attenuated the loss of cell viability, ROS generation, lipid peroxidation, and cell apoptosis in glutamate-injured PC-12 cells. Conclusion: Our results indicate that A. absinthium extract protects PC12 cells against glutamate-induced injury, possibly by reducing oxidative stress and apoptosis.

Background: Osteosarcoma (OS) is the most prevalent primary bone sarcoma in the global child and young adult population, and the current mainstream treatment regimens are not very effective. The unique efficacy of traditional Chinese medicine (TCM) for cancers has recently received increasing attention. Oldenlandia diffusa (OD) is commonly used as adjuvant therapy for various cancers in Chinese herb medicine (CHM) with its unique pharmacological activities, but its therapeutic effect as well as the underlying mechanism against OS has yet to be systematically investigated. Objective: This study aims to find the underlying active mechanism of OD against OS. Methods: The candidate ingredients as well as drug targets of OD were obtained from the Traditional Chinese Medicine System Pharmacology (TCMSP) database, respectively. Meanwhile, the OS diseaserelated targets were acquired from GeneCards and MalaCards online databases. Then, by using Venny 2.1, the common key targets were imported into the STRING database to acquire their interaction relationship, and imported this PPI network file (.csv) into Cytoscape 3.6.0 software and merged to obtain PPI network intersections. Meanwhile, the MCODE plugin of Cytoscape was also used to further trim the core therapeutic targets. GO and KEGG enrichment and molecular docking analyses were performed to predict the underlying mechanism of OD against OS. Furthermore, in silico analysis results were validated by a series of cellular functional and molecular biological assays. Results: A total of 131 putative targets were identified to be involved in the anti-OS activity of OD. The PPI network, GO as well as KEGG analyses revealed that the 18 core targets were closely related to cell proliferation, apoptosis. Importantly, the subsequent in vitro assays verified that the suppressive effect of OD on OS cell growth indeed resulted from disrupted apoptosis and cell proliferation via Akt and ERK signaling pathways. Furthermore, our results showed that quercetin, beta-sitosterol and 2-methoxy-3- methyl-9,10-anthraquinone were the key ingredients, while PTGS2, CASP3 and JUN were the key targets in delivering the pharmacological activities of OD against OS, thus providing an insight into the anti-OS action of OD from a holistic perspective. Conclusion: In summary, our results indicate that OD has good prospects in the treatment of OS.

Background: Most of the structural modifications to evodiamine (EVO) have focused on the 3- and 10-positions, while structural modifications to the EVO 2-position have not yet been reported. In this study, we investigated the scaffold diversity and bioactivity of EVO from position 2 to gain more insight into the influence of the chemical space around EVO on bioactivity. Objective: The study aims to synthesize two derivatives of EVO with hydroxy groups, 8a and 8b, and to investigate the antitumor activity of EVO derivatives with hydroxy groups compared to EVO. Methods: The synthesized compounds were structurally characterized by ¹H NMR, ¹³C NMR, and mass spectrometry. The effects of compounds 8a, 8b, and EVO on the proliferation of H460, A549, and Eca109 cells in vitro were determined by MTT. The effect of EVO, 8a and 8b on apoptosis of H460 cells was investigated by the annexed V-FITC/propidium iodide (PI) combination assay. The expression of EVO, 8a and 8b on apoptosis-related proteins was examined by Western blot analysis. To simulate the binding ability between small molecules and proteins, molecular docking calculations of EGFR^WTand EGFR^T790M with 8a and 8b, respectively, were performed using Schrödinger software. Results: In the cytotoxicity assay, compound 8b showed lower IC50 values for the three tumor cell lines (6.69 μM for H460 cells, 20.02 μM for A549 cells, and 16.47 μM for Eca109 cells) compared to compound 8a and EVO, and 8b induced apoptosis by affecting apoptosis-related proteins CRAF, AKT, and ERK in a late apoptotic manner. The molecular docking results showed that 8b has a good binding ability to EGFR upstream of apoptosis-related proteins. Conclusion: These findings suggest that 8b has significantly higher antitumor biological activity than EVO and 8a. This antitumor effect has important implications for the study of EVO derivatives in antitumor models.

Background: Rapidly dissolving oral strips have many advantages, especially in pediatric and geriatric use. Benzydamine hydrochloride is an active substance with local analgesic, anesthetic, antimicrobial and non-steroidal anti-inflammatory properties. Objective: The aim of the study was to formulate and characterize orally dispersible benzydamine hydrochloride- loaded fast dissolving oral strips for the sufficient treatment of oral mucositis with high loading capacity as well as high patient compliance considering ease of use. Methods: Oral strips were prepared by solvent casting method with many different polymer combinations and evaluated for different characteristics. In vitro and ex vivo characterizations were performed. Results: In appearance oral strips were smooth and they were also uniform in thickness and weight. The release rates of the active agent from oral strips reached 100% within 25 minutes. The disintegration time was within the range of 15.5 ± 1.2 seconds. Due to ex vivo permeation studies steady-state flux of benzydamine hydrochloride in simulated saliva and pH 6.8 were found to be 27.1 μg cm⁻²h⁻¹± 1.4 and 26.2 μg cm⁻²h⁻¹± 1.7, respectively. No significant difference (p#131;0.05) in permeability studies was observed using pH 6.8 phosphate buffer compared to simulated saliva. Conclusion: Active agent was successfully loaded into the strips and the targeted system was successfully performed. Benzydamine hydrochloride as oral strips can be a better solution for the efficient treatment of oral mucositis for cancer patients during chemotherapy and radiotherapy stages.

Background: Angiogenesis is a natural and complex mechanism that is regulated by biomolecules formed by the body. Medicinal inorganic chemistry is increasing in popularity due to metal-based compounds, offering significant chances and possibilities for building novel anti-cancer medicines with promising anti-angiogenic effects. Objective: This study aimed to examine the successful results obtained from treatments with nanoparticle formulations of active drug substances. Methods: The nanoprecipitation/solvent displacement approach, with some changes, was used to make PLGA-based NPs. Result: The particle size obtained in the blank formulation was 82.4-473.9 nm, while the particle size in the API-loaded NPs was 193.2-678.0 nm. Among the formulations, NP-950-P, NP-390-P, and NP-350- CSP2 were found to have significant antioxidant potentials with IC50 values of 3.025, 5.198, and 7.4242 μg.mL^-1, respectively, when compared to Vit C. According to the microscopic evaluations, NP-950-P (including Pd(PyCrbx)2Cl2 as 50 μg.pellet-1) and NP-950-CSP2 (including Pd(PyCrbx)2Cl2 as 50 μg.pellet-1) showed strong anti-angiogenic effect whereas the other NP formulations showed weak antiangiogenic effect when compared with the positive control (±)-Thalidomide at the concentration of 50 μg.pellet^-1. Conclusion: When the results were examined, it was found that nanoscale drug carrier systems were prepared, and high antioxidant activity and anti-angiogenesis activity were detected, especially in nanoparticles prepared with 950. As per our knowledge, it is the first study in this field that will bring a new perspective to cancer treatment.