Current drug discovery technologies最新文献

{"title":"Design, <i>In Silico</i> Molecular Docking, and ADMET Prediction of Amide Derivatives of Chalcone Nucleus as EGFR Inhibitors for the Treatment of Cancer.","authors":"Shital Patil, Vrushali Randive, Indrani Mahadik, Kalyani Asgaonkar","doi":"10.2174/0115701638263890231027071518","DOIUrl":"10.2174/0115701638263890231027071518","url":null,"abstract":"<p><strong>Background: </strong>Cancer is a devastating disease. Many studies have shown that the primary causes of the aggressive and resistant types of cancer are the overexpression of receptors and growth factors, activation of oncogenes, and the inactivation of tumour suppressor genes. One such receptor is the epidermal growth factor receptor (EGFR), which is used as a drug target for the treatment of cancer.</p><p><strong>Objective: </strong>This study aimed to develop the new chemical entities of amide derivatives of chalcone as EGFR inhibitors using structure-activity relationship (SAR) studies, molecular docking, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) studies.</p><p><strong>Method: </strong>New chemical entities (NCE) were designed based on literature findings. The Schrodinger 13.4 software was used for the molecular docking study. While Quickprop and Pro Tox-II online tools were used for ADME and toxicity prediction, respectively. .</p><p><strong>Result: </strong>In this work, all compounds were subjected to an <i>in-silico</i> ADMET analysis. After pharmacokinetic and toxicity profile predictions, the molecules were further analysed by molecular docking. As a result of molecular docking, molecules AC9 and AC19 showed comparable docking scores compared to standard Afatinib.</p><p><strong>Conclusion: </strong>Molecules AC9 and AC19 showed good docking scores and a promising ADMET profile. In the future, these derivatives can be further evaluated for wet lab studies and determination of their biological activity.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"9-19"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71430437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis, Characterisation, and Evaluation of Substituted Quinolin-2-one Derivatives as Possible Anti-lung Cancer Agents.","authors":"Riya Swar, Prachita Gauns Dessai, Shivalingrao MamleDesai, Sachin Chandavarkar, Soniya Phadte, Bheemanagouda Biradar","doi":"10.2174/0115701638258479231220051227","DOIUrl":"10.2174/0115701638258479231220051227","url":null,"abstract":"<p><strong>Background: </strong>According to 2022, the estimated number of cancer cases in India was found to be 1,461,427. Lung cancers are the leading cause of death among Indian males. Research on cancer has been conducted to develop better treatments that are safe and effective and could be used to diagnose cancer at an early stage. It was found that quinolin-2-one possesses anticancer activity, which led us to synthesize substituted quinolin-2-one derivatives that can provide a longer future to cancer patients and decrease the risk of dying from cancer.</p><p><strong>Objective: </strong>This study aimed to carry out the design, synthesis, characterisation, and evaluation of novel substituted quinolin-2-one analogues as possible anti-lung cancer agents.</p><p><strong>Methods: </strong>Compound III a/III b on reaction with acids, sodium acetate and ethylchloroacetate, substituted benzaldehyde, phthalic anhydride, and 2N sodium hydroxide yielded compounds IV a/ IV b, V a/ V b, VI a/ VI b, VI c/ VI d, VI e/ VI f, VII a/ VII b, and VIII a/ VIII b, respectively.</p><p><strong>Result: </strong>Among all the synthesised derivatives, compound VII a was found to be most potent with a MolDock score of -132.78 as compared to standard drug imatinib (-114.37) and active ligand 4- anilinoquinazoline (-126.71). All the synthesized derivatives showed a good ADME profile, but compound VII a showed the best ADME data among all the synthesised derivatives. All the synthesised compounds were tested for their <i>in vitro</i> anticancer activity against the Hop-62 (human lung cancer) cell line, out of which compound VII a was found to be most potent, with a percent control growth of -51.7% at a concentration of 80 μg/ml, which was in comparable to the positive control, Adriamycin (-70.5%) and standard imatinib (-84.0%).</p><p><strong>Conclusion: </strong>Compound VII a showed the highest MolDock score and was most potent against human lung cancer cell line Hop-62.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"e261223224851"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence for the Management of Breast Cancer: An Overview.","authors":"Harshita Gandhi, Kapil Kumar","doi":"10.2174/0115701638262066231030052520","DOIUrl":"10.2174/0115701638262066231030052520","url":null,"abstract":"<p><p>Breast cancer is a severe global health problem, and early detection, accurate diagnosis, and personalized treatment is the key to improving patient outcomes. Artificial intelligence (AI) and machine learning (ML) have emerged as promising breast cancer research and clinical practice tools in recent years. Various projects are underway in early detection, diagnosis, prognosis, drug discovery, advanced image analysis, precision medicine, predictive modeling, and personalized treatment planning using artificial intelligence and machine learning. These projects use different algorithms, including convolutional neural networks (CNNs), support vector machines (SVMs), decision trees, and deep learning methods, to analyze and improve different types of data, such as clinical, genomic, and imaging data for breast cancer management. The success of these projects has the potential to transform breast cancer care, and continued research and development in this area is likely to lead to more accurate and personalized breast cancer diagnosis, treatment, and outcomes.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"e031123223115"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Antioxidant Capacity of Newly Synthesized Flavonoids <i>via</i> DPPH Assay.","authors":"Umang Shah, Samir Patel, Mehul Patel, Sandip Patel","doi":"10.2174/0115701638284053240106123407","DOIUrl":"10.2174/0115701638284053240106123407","url":null,"abstract":"<p><strong>Background: </strong>Numerous naturally occurring and artificially synthesized flavonoids have garnered attention for their impressive ability to combat oxidative stress and scavenge free radicals when evaluated in laboratory settings. The core aim of our investigation revolved around assessing the antioxidant potential of a diverse range of synthesized flavonoids through <i>in vitro</i> experiments.</p><p><strong>Method: </strong>We crafted 29 distinct flavonoids using the aldol condensation mechanism via a chalcone intermediate to accomplish this. We meticulously characterized these newly formed compounds using a variety of spectroscopic techniques. We employed the widely recognized DPPH free radical method for the crucial antioxidant evaluation, a benchmark in such studies.</p><p><strong>Result: </strong>The radical scavenging efficacy of our synthesized flavonoids was then meticulously compared to that of the positive control, ascorbic acid, renowned for its antioxidant prowess, and the IC50 values for each compound were calculated and examined. Surprisingly, our results showed that the flavonoids we tested had a wide range of antioxidant activity, with IC₅₀ values that ranged from 75.8 ± 8.30 to 397 ± 25.10 μg/mL.</p><p><strong>Conclusion: </strong>Intriguingly, compounds US5, US13, US16, US17, US18, and US21 outshone even ascorbic acid in their antioxidant potential, displaying remarkable scavenging abilities against free radicals. This discovery holds promise for further exploration of these compounds as potential antioxidants with potential applications in health and wellness.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"e220124225850"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139522397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nutritional Profile, GC-MS Analysis and <i>In-silico</i> Anti-diabetic Phytocompounds Candidature of <i>Jatropha gossypifolia</i> Leaf Extracts.","authors":"Olasunkanmi Kayode Awote, Rahmon Ilesanmi Kanmodi, Success Chidera Ebube, Zainab Folashade Abdulganniyyu","doi":"10.2174/0115701638267143230925172207","DOIUrl":"10.2174/0115701638267143230925172207","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus (DM) is a metabolic disorder known to impair many physiological functions via reactive oxygen species (ROS). Aldose reductase, sorbitol dehydrogenase, dipeptidyl peptidase IV, α-amylase and α-glucosidase are pharmacotherapeutic protein targets in type-2 diabetes mellitus (T2DM). Inhibitors of these enzymes constitute a new class of drugs used in the management and treatment of T2DM. Some reports have claimed that medicinal plant extracts that serves as food (and as an antioxidant source) can reduce these alterations by eliminating ROS caused by DM. Ethnobotanical survey claims <i>Jatropha gossypifolia</i> commonly called \"fignut\" and \"Lapa-lapa\" in the Yoruba land of South-western Nigeria, to be used for the treatment and management of diabetes, in addition to its nutritive value.</p><p><strong>Objective: </strong>The nutritional composition and <i>in-silico</i> antidiabetic potential of the bioactive constituents of <i>J. gossypifolia</i> leaf extracts were investigated.</p><p><strong>Methods: </strong>Proximate, minerals and gas chromatography-mass spectroscopy (GC-MS) analysis were carried out using standard procedures. Phytocompounds present in J. gossypifolia methanol (JGM) and ethyl acetate (JGE) leaf extracts were tested as potential antagonists of selected protein targets <i>via in-silico</i> techniques. Drug-likeness, pharmacokinetic properties and toxicity of the promising docked ligands were also predicted.</p><p><strong>Results: </strong>The proximate and mineral analysis revealed good nutritional composition and mineral content. Additionally, cyclo-pentadecane and dibutyl phthalate from methanol extract, and benzene- 1,2,4,5-tetramethyl, benzene-1,2,3,5-tetramethyl, and benzene-1,3-dimethyl-5-(1-methylethyl) from ethyl acetate extract were present in J. gossypifolia leaf which exhibited a better binding affinity than the clinically prescribed standard, metformin.</p><p><strong>Conclusion: </strong>Benzene-1,2,4,5-tetramethyl from JGE extracts exhibited the most promising antidiabetic potential <i>in-silico</i>, suggesting its candidature as diabetes-target-protein inhibitor which may be developed for the treatment of type-2 diabetes mellitus.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"32-45"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41223890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Spinacia Oleracea</i>: Exploring the Therapeutic Potential in Persian Medicine and Modern Pharmacology.","authors":"Fatemeh Akbari, Melika Mollaei, Pendar Argani, Babak Daneshfard, Ali Reza Derakhshan","doi":"10.2174/0115701638275971240201060710","DOIUrl":"10.2174/0115701638275971240201060710","url":null,"abstract":"<p><strong>Background: </strong>Spinach is a widely cultivated dark leafy vegetable highly regarded for its medicinal properties in traditional Persian medicine. It is rich in vitamins, minerals, flavonoids, carotenoids, and other bioactive compounds, and this review aims to explore the historical applications of spinach in Persian medicine and juxtapose them with current scientific evidence. Despite its historical significance, there remains a need to comprehensively evaluate and integrate traditional knowledge with modern research on the therapeutic benefits of spinach.</p><p><strong>Methods: </strong>To achieve this, a comprehensive search was conducted in Persian medicine references and scientific databases to gather information on the traditional uses, chemical composition, and pharmacological effects of spinach. Studies that met the inclusion criteria were meticulously categorized, and relevant data were analyzed to draw insightful comparisons.</p><p><strong>Results: </strong>Persian medicine describes spinach as a nutrient-rich, laxative, and fast-digesting agent with therapeutic effects on inflammation, lung diseases, back pain, sore throats, jaundice, urinary disorders, joint pain, eye inflammation, insomnia, dementia, and more. Modern studies have substantially corroborated these traditional uses, revealing that spinach possesses antioxidant, anti-inflammatory, anti-cancer, blood sugar-lowering, lipid-lowering, anti-obesity, neurological, ocular, and musculoskeletal effects.</p><p><strong>Conclusion: </strong>Spinach exhibits a wide range of beneficial effects on various health conditions. Its widespread availability, low cost, and exceptional nutritional richness position it as a promising candidate for further investigation. Future studies should explore the clinical effectiveness of spinach in various diseases, while taking into consideration the principles emphasized in Persian medicine to guide research and inform therapeutic strategies.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"e150224227025"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological Activities of Zinc Oxide Nanoparticles Green Synthesized Using the Aqueous Extract of <i>Dracocephalum kotschyi</i> Boiss.","authors":"Foroogh Mirzania, Iraj Salimikia, Javad Ghasemian Yadegari, Abdolrazagh Marzban, Amirmasoud Firouzi, Alireza Nazarzadeh, Javid Aalaei","doi":"10.2174/0115701638284118231220074251","DOIUrl":"10.2174/0115701638284118231220074251","url":null,"abstract":"<p><strong>Background: </strong><i>Dracocephalum kotschyi</i> Boiss. is known as a native medicinal plant of Iran.</p><p><strong>Objective: </strong>In this study, aqueous extract of <i>D. kotschyi</i> was used to synthesize ZnO-NPs. To produce ZnO-NPs, aerial parts of <i>D. kotschyi</i> were powdered and then macerated for obtaining aqueous extract, after that, aqueous extract was used to reduse zinc nitrate to ZnO-NPs.</p><p><strong>Methods: </strong>To confirm nanoparticles synthesis, SEM, TEM, UV-Vis, FTIR, and XRD were used. The synthesized ZnO-NPs were studied for antimicrobial activities by microdilution method for calculating MIC and MBC. Analysis of ZnO-NPs confirmed successful synthesis by extract of D. kotschyi.</p><p><strong>Results: </strong>The sizes of ZnO-NPs were estimated 50-200 nm in diameter. Antibacterial and antifungal experiments showed potent activities against <i>Staphylococos aureus</i>, Pseudomonas aeruginosa and Candida albicans. The results of the studies showed that the nanoparticles synthesized with the aqueous extract of <i>D. kotschyi</i> have a much greater antimicrobial effect than the aqueous extract of D. kotschyi and zinc nanoparticles, each alone (MIC values 3.7 to 7.5 mg/ml).</p><p><strong>Conclusion: </strong>The noteworthy point is that the inhibitory rate of synthesized zinc oxide nanoparticles is higher compared to broad-spectrum antibiotics, such as chloramphenicol (MIC values 15 mg/ml). Determining the therapeutic and toxic dose of this product for humans requires further investigation and clinical trials.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"e271223224899"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Niosomal Encapsulation of Quercetin and Silymarin and their Combination on Dimethylnitrosoamine-induced and Phenobarbital promoted Hepatocellular Carcinoma in Rat Model.","authors":"Devendra S Shirode, Dinesh J Raut, Nikita Sarasawat","doi":"10.2174/0115701638278205231231153851","DOIUrl":"10.2174/0115701638278205231231153851","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma is a particularly dangerous and severe kind of liver cancer. Many anticancer drugs fail to complete the treatment of hepatocellular carcinoma without any side effects. There should be appropriate and without side effective treatments for hepatocellular carcinoma.</p><p><strong>Objective: </strong>The objective of the current study was to evaluate how quercetin and silymarin in a niosomal formulation affected hepatocyte carcinoma caused by diethylnitrosamine.</p><p><strong>Methods: </strong>Five groups were created from the thirty male rats. Normal control (untreated group), tumor group (administered dimethylnitrosoamine 200 mg/kg), treatment group I (administered 50 mg/kg of niosomal encapsulated quercetin), treatment group II (administered 50 mg/kg of niosomal encapsulated silymarin), and treatment group III (administered 50 mg/kg of niosomal encapsulated quercetin + silymarin). Then, biochemical estimation, serum analysis, and histopathological examination were carried out.</p><p><strong>Results: </strong>Treatment group III, treated with niosomal encapsulation of a combination of quercetin + silymarin 50 mg/kg, demonstrated the significant restoration of alpha-fetoprotein and carcinoembryonic antigen and also antioxidants like superoxide dismutase and nitric oxide. The histopathological examination showed improved liver architecture in this group compared to other treatment groups.</p><p><strong>Conclusion: </strong>Our findings revealed that a potent anticancer effect was observed in treatment group III as niosomal formulation increased the bioavailability of the drug within the body. In order to completely understand the underlying processes and evaluate the therapeutic effectiveness of these chemicals in the therapy of hepatocellular carcinoma, further investigation and clinical trials are required.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"e250124226254"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139567703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulation Induced in BALB/c Mice after Subacute Exposure to Hydroalcoholic Extract of <i>Artimisia Dracunculus</i>.","authors":"Fatemeh Forouzanfar, Seyed Mostafa Moshirian Farahi, Hassan Rakhshandeh, Bahram Memar, Roghayeh Rashidi, Ramin Mahdipour, Bamdad Riahi-Zanjani","doi":"10.2174/0115701638279953231222062644","DOIUrl":"10.2174/0115701638279953231222062644","url":null,"abstract":"<p><strong>Introduction: </strong>Tarragon, with the scientific name of <i>Artemisia dracunculus</i>, is a perennial herbaceous plant with a wide spectrum of pharmacologic properties. In the current investigation, BALB/c mice were used to examine the immunomodulatory effects of hydroalcoholic extract of tarragon (HET).</p><p><strong>Methods: </strong>Mice were treated with hydroalcoholic extract of <i>Artimisia dracunculus</i> (HET) at two doses (250 and 500 mg/kg) for 14 days. The host hematological parameters, spleen cellularity histopathology, hemagglutination titer assay (HA), delayed-type hypersensitivity (DTH) responses, IFN-γ and IL-4 levels produced by spelenocytes, and the proliferation of lymphocytes were assayed.</p><p><strong>Results: </strong>HET at a high dose significantly could increase the number of white blood cells and lymphocytes compared to the control group. The lymphocyte proliferation in exposure to PHA significantly increased in the HET group at both doses compared to the control group, whilst this index in the presence of LPS increased significantly for the 500 mg/kg-HET group only. Moreover, in the HA and DTH tests, HET significantly increased the proliferation of lymphocytes as compared with the control group. Furthermore, HET significantly increased the amount of IFN-γ parallel to a decrease in the level of IL-4 in compared to the control group.</p><p><strong>Conclusion: </strong>Based on our findings, HET has potent immunostimulant characteristics. More investigation into tarragon's potential to be used in the treatment of disorders caused by a weakened immune response should be conducted.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"e240124226142"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139567719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Docking, Characterisation, and Synthesis of Pyrimidine Derivatives for Antidepressant Activity.","authors":"Ashwini Jadhav, Sunil G Shingade, Prachita G Dessai, Bheemanagouda S Biradar, Shivalingrao MamleDesai","doi":"10.2174/0115701638243835230925161546","DOIUrl":"10.2174/0115701638243835230925161546","url":null,"abstract":"<p><strong>Background: </strong>According to the report, in 2022, the prevalence rate of depression in India was 4.50%, and the cases stood at 56,675,969. The development of antidepressant agents has reduced the number of depressant and suicidal cases. Many researchers have found that pyrimidine possesses antidepressant activity. With this background, we thought of synthesizing pyrimidine derivatives.</p><p><strong>Objective: </strong>The objective of this study is to carry out molecular docking, synthesis, characterization, and evaluation of 2-((4,6-diphenylpyrimidin-2-yl)oxy)-N-phenylacetamide derivatives (17-26) as in vivo antidepressant agent.</p><p><strong>Method: </strong>The designed compounds were checked for their activity using Molegro virtual docker (MVD) and were further synthesized. Benzaldehyde reacted with acetophenone to give compound (3), which gave compound (4) upon reaction with urea. In another reaction, substituted anilines (5) were reacted with chloroacetyl chloride (6) to yield compounds (7-16), which upon further reaction with compound (4) yielded the final derivatives (17-26). The synthesized compounds were characterized by spectral analysis and checked for their antidepressant activity.</p><p><strong>Result: </strong>The MolDock scores of the derivatives ranged from -147.097 to -182.095, whereas of active ligand IXX_801 was -115.566. All the synthesized pyrimidine derivatives showed better affinity towards the Cryo-EM structure of the wild-type human serotonin transporter complexed with vilazodone, imipramine, and 15B8 Fab protein (PDB ID: 7LWD) as compared to standard drug clomipramine (-101.064). All the synthesized derivatives were screened for antidepressant activity at a 100mg/kg dose level compared to the standard clomipramine HCl at a dose level of 20mg/kg. Among all the synthesized derivatives, compound 24 showed the most potent antidepressant activity, and Compound 20 showed moderate antidepressant activity, which reduced the duration of immobility times to 35.42% and 31.97% at 100mg/kg dose level when compared to the control, respectively.</p><p><strong>Conclusion: </strong>Compound 24 showed the highest MolDock score as well as found to be the most potent antidepressant agent.</p>","PeriodicalId":93962,"journal":{"name":"Current drug discovery technologies","volume":" ","pages":"64-72"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49686489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}