Letters in Drug Design & Discovery最新文献

{"title":"Development of Potential Antidiabetic Agents Using 2D and 3D QSAR, Molecular Docking and ADME Properties In-silico Studies of α-Amylase Inhibitors","authors":"Kalusing S. Padvi, Aniket P. Sarkate, Shashikant V. Bhandari, Mahadevi V. Kendre","doi":"10.2174/0115701808279839240206123454","DOIUrl":"https://doi.org/10.2174/0115701808279839240206123454","url":null,"abstract":"Background: A series of 2-arylbenzimidazole derivatives were designed and developed as antidiabetic drugs using 2D and 3D QSAR, molecular docking and ADME studies. background: A series of 2-arylbenzimidazole derivatives were designed and developed as antidiabetic drugs using 2D and 3D QSAR, molecular docking and ADME studies. Methods: All molecular modeling studies were performed using Molecular Design Suite V-Life MDS software. New chemical entities (NCEs) were designed based on the results of 2D and 3D QSAR studies. Docking studies were performed with the designed NCEs in PDB: 5E0F and the results were compared with the receptor ligand. According to the ADME results, all the proposed compounds have good oral absorption, correct molecular weight, QPlogPo/w. All units show oral absorption above 80%, it is considered well absorbed. All the proposed units show satisfactory results in the area. This indicated that these NCEs have little or no chance of failure in the final stages of the drug development process. Results: The 2D QSAR results showed that the descriptor k2alpha, T_T_N_5, IodinesCount and BrominesCount play the most important role in determining the inhibitory activity of α-amylase. Although 3D QSAR showed that, the q2 and Pred_r2 values of the model (SA kNN MFA model) were 0.7476 and 0.6932. The G score of the proposed compound numbers mol-1, mol-2, mol-3, mol- 4, mol-5, mol-6, mol-7 and mol-8 are better compared to the standards, indicating that the proposed compounds have good binding properties affinity to bind to α-amylase. Conclusion: These investigations have produced statistically significant and exceptionally reliable 2D and 3D Quantitative Structure-Activity Relationship (QSAR) models for antidiabetic medications, particularly α-amylase inhibitors. Furthermore, docking experiments involving the α-amylase enzyme have revealed that the binding energies of most Novel Chemical Entities (NCEs) are comparable to those of the established standards. Docking studies with α-amylase enzyme showed that most NCEs have binding energies comparable to the standard.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"24 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140010057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico Structure-based Screening of Potential Anticancer Bioactive Natural Constituents from African Natural Products","authors":"Khairedine Kraim, Atidel Boudjedir, Youcef Saihi, Fatima Zohra Oueld Chikh, Yassira Slatnia, Fouad Ferkous","doi":"10.2174/0115701808280302240117055932","DOIUrl":"https://doi.org/10.2174/0115701808280302240117055932","url":null,"abstract":"Introduction: Inhibitors of topoisomerases, essential regulators of cancer development, are promising as cancer treatments. These enzymes regulate DNA topology and eliminate topological constraints during various biological processes, including replication, transcription, and recombination. Nature has continually offered scientists pathways to explore the development of new drugs. Indeed, since ancient times, various plant extracts have been utilized in treating multiple pathologies. Objective: It’s intriguing to diversify the therapeutic classes of natural topoisomerase 1 inhibitors. We aimed to explore the relationship between the toxicity of certain medicinal plants in North Africa and their anti-topoisomerase 1 enzyme activity. This investigation aims to discover potentially valuable compounds for fighting cancer by inhibiting the Topo1 enzyme, enriching the anticancer therapeutic class. Methods: This study has conducted a virtual screening of the African Natural Products Database to identify new scaffolds as topoisomerase 1 inhibitors. Molecular docking as a structure-based drug design approach was selected as one of the best approaches, and the complex code ID: 1K4T was used for this purpose. Results and Discussion: The molecular docking of more than 5790 natural products extracted from this database was docked into the binding site of the above-cited complex using the Modlock optimizer and Moldock score as search and scoring function algorithms, respectively. The top-ranked compounds have been assessed, analyzed, and compared to Topotecan and Irinotecan as reference ligands and drugs. Conclusion: Consequently, the seven natural products have shown a strong affinity to topoisomerase 1 and DNA. They establish a clear link between topoisomerase 1 inhibition and the anticancer activity of their corresponding plant extracts. Therefore, these hits are promising and serve as a base for further development of new topoisomerase 1 inhibitors.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"245 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139756175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Essential Structural Profile of Novel Adenosine Derivatives as Antiplatelet Aggregation Inhibitors based on 3D-QSAR Analysis","authors":"Shunlai Li, Pengyu Zheng, Yajing Ren, Hongguang Du","doi":"10.2174/0115701808247583231124062525","DOIUrl":"https://doi.org/10.2174/0115701808247583231124062525","url":null,"abstract":"Aims: In this research, 3D-QSAR evaluation on a set of fresh purinoid compounds that we produced was conducted. This analysis aims to illustrate the correlation between the structure of purine and its ability to prevent platelet aggregation. Our findings could pave the way to discovering novel antithrombotic medications. background: Cardiovascular disease caused by platelet aggregation is a serious threat to human health. Purine derivatives are important molecules with antiplatelet aggregation activity. Background: The incidence of cardiovascular disease triggered by the clumping of platelets poses a significant danger to human health. Purine derivatives are important molecules with antiplatelet aggregation activity. Objective: The objectives of this research are to establish the correlation between the structure of purine and its ability to prevent platelet aggregation. Such a correlation could aid in the development of innovative antithrombotic medications. method: In this study, 3D-QSAR analysis was performed on a series of novel purine derivatives synthesized by us based on comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). Methods: In this study, 3D-QSAR investigation on a collection of 75 new purine derivatives, which we synthesized, was conducted, utilizing Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). result: Significant correlation coefficients (CoMFA, q2=0.843, r2=0.930, F value=266.755, SEE=0.165; CoMSIA, q2=0.869, r2=0.918, F value=222.571, SEE=0.179) were obtained, and the model prediction ability was validated using the test set. Results: Significant correlation coefficients (CoMFA, q2= 0.843, r2= 0.930, F value= 266.755, SEE= 0.165; CoMSIA, q2= 0.869, r2= 0.918, F value= 222.571, SEE= 0.179) were obtained, and assessed the model's predictive capabilities by validating it with the test set. conclusion: The results suggest that it is beneficial to introduce a group of appropriate size at position C-2 of the purine ring, and that an excessively large group is disadvantageous; a bulky substituent group cannot be directly attached at the C-6 position of the purine ring, and the attachment of a group with low electron cloud density increases the activity, and the attachment of a bulky group at the C-5' of the sugar ring is beneficial, and the presence of hydrogen bond receptors in this region also increases the activity. Conclusion: Our findings indicate that the introduction of an appropriately sized structure at position 2 of the compound yields significant benefits. Conversely, the attachment of an excessively large group is detrimental. Direct attachment of a bulky substituent at C-6 of the compound is not feasible, and its activity increases when the structure with low electron cloud density is added. Moreover, the presence of a voluminous functional group at the 5' position of the compound is advantageous, and its ","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"17 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139670315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Review of the Advancement in Omic Technologies in the Field of Drug Discovery and Development","authors":"Mridula Chauhan, Shivansh Kumar, Arpon Biswas, Mukesh Kumar, Sarvesh Kumar Verma, Anjali Mishra, Vaishali Singh, Amol Chhatrapati Bisen, Sristi Agrawal, Abhijit Deb Choudhury, Ramkrishna Rayiti, Rabi Sankar Bhatta","doi":"10.2174/0115701808287654240126112003","DOIUrl":"https://doi.org/10.2174/0115701808287654240126112003","url":null,"abstract":": Discovering new drugs is time-consuming and expensive and involves many different tools from various domains. Numerous omic technologies, such as genomics, transcriptomics, proteomics, and metabolomics, have been created to speed up the process. Leveraging genetic and genomic insights, these methodologies play a pivotal role. Genetic insights aid in target identification, prioritization, and the prediction of drug outcomes. Gene expression data informs drug discovery, while proteomics uncovers targets and facilitates high-throughput profiling. Enhancing drug efficacy necessitates mechanistic insights into downstream effects, enabling side effects and resistance prediction. Early-stage drug discovery now extensively employs diverse metabolomics platforms. This review underscores the recent strides of omic technologies in drug discovery, affirming their role in enhancing drug viability and regulatory approval. The emphasis lies on the latest advancements in genomics, transcriptomics, proteomics, and metabolomics, collectively fortifying drug development.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"10 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139665512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Voyage of Graphene-based Biosensor","authors":"Rama Sharma","doi":"10.2174/0115701808291102240130113741","DOIUrl":"https://doi.org/10.2174/0115701808291102240130113741","url":null,"abstract":": The study of carbon-based materials and nanoparticles is currently an exciting field of study in the domain of material science. One of the most prominent of these materials is graphene, along with its related components graphene oxide and reduced graphene oxide. A single-layer, twodimensional nanomaterial called graphene (GN) is employed in many different industries, such as electronics and biology. Graphene is a remarkable two-dimensional substance that has earned the title of \"wonder material.\" Its remarkable electrical, optical, thermal, and mechanical qualities have attracted significant attention. Graphene's intriguing characteristics have led to its integration into numerous biosensing applications. Graphene possesses remarkable chemical, electrical, and physical qualities. The distinctive properties of graphene, particularly its electrical conductivity, large surface area, and significant electron mobility, are focusing more attention on applications in biomedicine that facilitate easier health monitoring. Biosensors with high sensitivity and precision can enhance patient care, and offer an opportunity for an early illness diagnosis and clinical pathogen identification. Additionally, a wide range of biological molecules, including glucose, hydrogen peroxide, cholesterol, dopamine, etc., can be detected using graphene-based biosensors. This study evaluates contemporary developments regarding graphene-based biosensors and their prospects and difficulties in this rapidly developing profession in the coming era. Graphene-based nanomaterials are appropriate to be employed in various biological and sensory contexts, including medicine and gene transfer, because of their unusual topologies and extraordinary properties. Graphene's outstanding characteristics enable biosensing applications to obtain the appropriate sensitivity, selectivity, and repeatability for a range of targets.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"3 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139663132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QSAR Analysis and Molecular Docking Studies of Aryl Sulfonamide Derivatives as Mcl-1 Inhibitors and the Influence of Structure and Chirality on the Inhibitory Activity","authors":"Jia Chen, Yang Ma, Jian-Wei Zou, Sheng Hu, Meilan Huang, Guixiang Hu","doi":"10.2174/0115701808278918240109053316","DOIUrl":"https://doi.org/10.2174/0115701808278918240109053316","url":null,"abstract":"Background:: Mcl-1 is a kind of antiapoptotic protein and its overexpression is closely related to the occurrence of cancer. Aryl sulfonamide derivatives are expected to become new anticancer agents due to their high inhibitory activity on the Mcl-1 protein. Objective:: The study aimed to establish the QSAR model with good prediction ability and elaborate the influence of structure and chirality on the inhibitory activity. method: Multiple QSAR models were built with different types of descriptors and modeling methods. The molecular docking was performed on compound 45, 25, 26, 24R and 24S. Results:: The comprehensive models including 2D and 3D descriptors demonstrated that nonlinear LSSVM and GP methods gave better results (R2>0.94, RCV2>0.86). The training set had a good predictive power on the test set. The predictive performances of MCCV tests are basically coincident with the results of the single test set. The results of molecular docking showed that the hydrogen bond acceptor at the appropriate position of the substituent on the chiral center can form the hydrogen bond interaction with residue ASN260, which results in the stronger interaction between ligand and protein and higher inhibitory activity. The interaction differences between R and S configuration with Mcl-1 protein are mainly attributed to two residues, HIS224 and ASN260. Two opposite effects lead to the activity of R enantiomer slightly higher than that of S one. The results on chiral compound 24 with ambiguous absolute configuration demonstrated that the steric effect of the substituents on chiral carbon atom is crucial. When there are two substituents with big volume at the same time, high steric effect will prevent the binding of the substituent and the protein, which results in the low inhibitory activity. Conclusion:: The study may provide theoretical guidance on the design and synthesis of novel aryl sulfonamide derivatives with high inhibitory activity","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"1 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139663544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Ginger, Cardamom, Purslane, Saffron and Cinnamon Consumption on Lipid Profile, Glycemic Control, Blood Pressure and Markers of Anthropometric and Inflammation in Metabolic Syndrome Patients: A Systematic Review and Network Meta-Analysis","authors":"Sajjad Salimi, Zahra Asgari, Tahereh Sadat Mousavi, Seyed Amir Karimi, Arezoo Hamidi, Shayan Mostafaei, Pardis Mohammadi Pour, Mohammad Hosein Farzaei","doi":"10.2174/0115701808270287240105092957","DOIUrl":"https://doi.org/10.2174/0115701808270287240105092957","url":null,"abstract":"Background:: Metabolic syndrome (MetS), also known as syndrome X or insulin resistance, is a complex disorder characterized by multiple risk factors. It is caused by insulin resistance, which is accompanied by abnormal accumulation and dysfunction of adipose tissue. Introduction:: Recently, several studies have evaluated the efficacy of herbs on MetS. The purpose of this meta-analysis is the comprehensive assessment of the impact of cardamom, cinnamon, saffron, purslane and ginger on the parameters of MetS in patients with MetS. Methods:: A systematic search was performed based on the English language reports of literature from databases including PubMed, Scopus, Cochrane, and Web of Science and 29 RCT (randomized clinical trial) studies were included in the meta-analysis. This meta-analysis was registered in PROSPERO. Results:: The results showed significant beneficial effects of cardamom on Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and waist circumference (WC), cinnamon on diastolic blood pressure (DBP) and weight, ginger on fasting blood sugar (FBS), Hemoglobin A1c HbA1c and HOMA-IR and purslane on triglyceride (TG), total cholesterol (TC), body mass index (BMI) and FBS compared to the placebo; thus, they can be useful in the management of patients with MetS. Conclusion:: It is suggested that more RCT studies should be performed on the factors affecting the efficacy of these plants on the parameters of the MetS.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"224 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139587479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crocin Potentiates Anti-tumor Properties of 5-FU by Regulating Cell Proliferation and Tumor Necrosis in Breast Cancer","authors":"Nastaran Rezaei, Abdulridha Mohammed Al-Asady, Milad Hashemzehi, Maryam Moradi Binabaj, Farzad Rahmani, Amir Avan, Moein Eskandari, Mohammad Jalili-Nik, Fereshteh Asgharzadeh, Seyedeh Elnaz Nazari, Mikhail Ryzhikov, Majid Khazaei, Seyed Mahdi Hassanian","doi":"10.2174/0115701808258032231204080133","DOIUrl":"https://doi.org/10.2174/0115701808258032231204080133","url":null,"abstract":"Introduction:: Breast cancer is one of the most prevalent malignancies among women around the world. Crocus sativus, a natural food coloring and flavoring, has potent anti-tumor properties. The aim of the current study was to investigate the therapeutic potential of crocin, the main pharmacological active component of saffron, either alone or in combination with the standard chemotherapeutic treatment, 5-FU, in Breast cancer (BC) progression in both cellular and animal models. Material and Methods: MTT, Real-Time PCR, Western Blotting, Hematoxylin and eosin (H&E) tissue staining were applied to determine the anti-tumor properties of crocin in in vitro and in vivo samples. Results:: Our findings showed that crocin decreased breast cancer cell proliferation by suppressing cyclin D1 expression and Wnt/β-catenin signaling activation. Moreover, this molecule improved 5- FU anti-cancer activities by decreasing the tumor volume and weight, increasing tumor necrosis, and suppressing tumor inflammation in an animal model. Inflammation-associated anti-cancer activity of crocin is mediated by the down-regulation of pro-inflammatory genes, including IFN-γ and IL-1β, as well as inhibition of oxidative stress responses within the tumor environment. Conclusion:: This is the first study demonstrating the potent anti-tumor properties of crocin against BC progression. Our results suggest that this effective and low-toxic molecule could be a promising agent for reducing BC tumor progression when administered either alone or in combination with standard treatment in breast cancer patients.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"23 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of Some Novel 4-bromobenzoic Acid Clubbed Hydrazone Schiff Base Derivatives as Potent α-amylase Inhibitors: In vitro and In silico Studies","authors":"Momin Khan, Faima Alam, Aftab Alam, Abdul Wadood, Sulaiman Shams, Mehboob Ali, Sana Shah, Abullah F. AlAsmari, Metab Alharbi, Fawaz Alasmari","doi":"10.2174/0115701808262821231114114237","DOIUrl":"https://doi.org/10.2174/0115701808262821231114114237","url":null,"abstract":"Aims:: Synthesis of novel 4-bromobenzoic acid-based hydrazone-Schiff base derivatives and to screen them for their α-amylase inhibitory activity. Objective:: The biological activities of hydrazone-Schiff base compounds encouraged us to evaluate the synthesized derivatives (4-32) for in-vitro inhibition activity against the α-amylase enzyme. Methods:: In current research work twenty-nine Schiff base derivatives (4-32) of 4-bromobenzoic acid were synthesized in worthy yields by treating various replaced aldehydes with 4- bromobenzohydrazide using methanol solvent in catalytic quantity of acetic acid. The products were structurally described through the support of several spectroscopic methods (EI-MS and 1HNMR) and finally evaluated against α-amylase enzyme. Results:: All the made derivatives exhibited worthy inhibition potential from IC50 = 0.21 ± 0.01 to 5.50 ± 0.01 μM when equated to the usual acarbose drug having IC50 = 1.34 ± 0.01 μM. Compound 21 (IC50 = 0.21 ± 0.01 μM) was established as the most active inhibitor among the series better than standard. The structure-activity relationship study showed that the alteration in the activity of the produced products might be due to the attached position and nature of the substituents. Furthermore, in-silico study supported the effects of groups attached on the binding interaction with α-amylase enzyme. Conclusion:: A series of substituted hydrazone Schiff bases based on 4-bromobenzoic acid were produced, confirmed the structures by EI-MS and 1H-NMR spectroscopic methods and lastly tested for their in-vitro α-amylase inhibitory potential. Among the series, twenty-four products indicated brilliant inhibition potential having IC50 values from 0.21 ± 0.01 to 1.30 ± 0.01 μM. The structure-activity relationship study showed that the alteration in the activity of the synthesized products might be due to the attached position and nature of the substituents. On the other hand, in silico studies advocated that the synthesized Schiff base derivatives have prevalent interactions of binding within the active site of the α-amylase enzyme, and because of their various attached substituent, their conformation is altered in the active site of the enzyme. The current study recognized a number of lead candidates derived from 4-bromobenzoic acid. Additional investigation of the synthesized derivatives for coming research to get novel α-amylase inhibitors.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"11 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139462140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D and 2D-QSAR Studies on Natural Flavonoids for Nitric Oxide Production Inhibitory Activity","authors":"Chunqiang Wang, Yuzhu Fan, Minfan Pei, Chaoqun Yan, Taigang Liang","doi":"10.2174/0115701808179188231205064327","DOIUrl":"https://doi.org/10.2174/0115701808179188231205064327","url":null,"abstract":"Background: Nitric oxide (NO), an important second messenger molecule, regulates numerous physiological responses, while excessive NO generates negative effects on the circulatory, nervous and immune systems. Recently, some natural flavonoids were reported to possess the capability of inhibiting LPS-induced NO production. To fully understand the nature of their own NO inhibitory activity, it is necessary to address the structural requirements of flavonoids as NO inhibitors. Objective: The objective of this work was to develop efficient QSAR models for predicting the NOinhibitory activity of new flavonoids and improving insights into the critical properties of the chemical structures that were required for the ideal NO production inhibitory activities. Methods: To provide insights into the structural basis of flavonoids as NO inhibitors, 3D quantitative structure-activity relationship (3D-QSAR) and 2D-QSAR models were developed on a dataset of 55 flavonoids using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA) and hologram quantitative structure-activity relationship (HQSAR) approaches. method: CoMFA, CoMSIA combining HQSAR methods were employed on a series of flavonoids to generate 3D and 2D-QSAR models. Results: The statistically significant models for CoMFA, CoMSIA and HQSAR resulted in crossvalidated coefficient (q2) values of 0.523, 0.572 and 0.639, non-cross-validated coefficient (r2) values of 0.793, 0.828 and 0.852, respectively. The robustness of these models was further affirmed using a test set of 18 compounds, which resulted in predictive correlation coefficients (r2 pred) of 0.968, 0.954 and 0.906. Furthermore, the models-derived contour maps were appraised for activity trends for the molecules analyzed. result: Comparative Molecular Field Analysis (CoMFA), Comparative Molecular Similarity Indices Analysis (CoMSIA) combining hologram quantitative structure-activity relationship (HQSAR) methods were employed on a series of flavonoids to generate 3D and 2D-QSAR models. Result: The obtained models can be used to predict the activities of new flavonoids and identify the key structural features affecting the NO inhibitory activities. Conclusion: The 3D and 2D-QSAR models constructed in this paper were efficient in estimating the NO inhibitory activities of flavonoids and facilitating the design of flavonoid-derived NO production inhibitors. other: none","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":"29 1","pages":""},"PeriodicalIF":1.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139462171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}