Chemical Biology & Drug Design最新文献

{"title":"Rutecarpine Suppresses Non-Small Cell Lung Cancer Progression Through Activating the STING Pathway and Elevating CD8+ T Cells","authors":"Ze-Bo Jiang,&nbsp;Qing-Hua He,&nbsp;Li-Ping Kang,&nbsp;Sha Jiang,&nbsp;Jia-Ni Liu,&nbsp;Cong Xu,&nbsp;Wen-Jun Wang,&nbsp;Xuan-Run Wang,&nbsp;Qi-Biao Wu,&nbsp;Dong-Hui Huang","doi":"10.1111/cbdd.70070","DOIUrl":"https://doi.org/10.1111/cbdd.70070","url":null,"abstract":"<div>\u0000 \u0000 <p>Globally, non-small cell lung cancer (NSCLC) is the primary cause of cancer-related deaths. Rutecarpine (RUT), a quinazolinocarboline alkaloid that is naturally occurring and present in Chinese medicinal herbs, has been shown to have anticancer properties in several cancer cell lines. However, the specific antitumor mechanisms of RUT in NSCLC remain unclear. This study demonstrates that RUT induces apoptosis and significantly reduces the viability of NSCLC cell lines. This effect is achieved by stimulating intracellular ROS production, leading to mitochondrial dysfunction. The decreased cell viability observed with RUT treatment is attributed to the elimination of ROS and apoptosis through the suppression of ROS by N-acetylcysteine (NAC). Furthermore, RUT therapy elevated the production of CXCL10 and CCL5 in NSCLC cell lines and markedly activated the STING pathway in NSCLC cells. Mechanistically, RUT substantially decreased the levels of PD-L1 protein in NSCLC cells. Notably, in vivo experiments demonstrated that RUT significantly inhibits mouse NSCLC tumor growth in mice, exhibiting anti-tumor activity by elevating CD8⁺ T cells. These findings strongly support RUT as a promising anti-cancer drug for NSCLC.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475643","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":"Multiomics Analyses Demonstrate the Attenuation of Metabolic Cardiac Disorders Associated With Type 2 Diabetes by Stachydrine in Relation With the Transition of Gastrointestinal Microbiota","authors":"Chaoxing Yang,&nbsp;Huaping Zhong","doi":"10.1111/cbdd.70066","DOIUrl":"https://doi.org/10.1111/cbdd.70066","url":null,"abstract":"<div>\u0000 \u0000 <p>Stachydrine (STA) has therapeutic effects on heart disorders. The current study assessed its effects on Type 2 diabetes (T2D) induced cardiac disorders by focusing on the heart–gut axis. Mice were subjected to high-fat diet (HFD) and streptozocin (STZ) to induce cardiac disorders such as inflammation and structural deteriorations, which were handled with STA. Changes regarding the composition and metabolism of gastrointestinal (GI) microbiota were then determined using a multiomics strategy, including amplicon sequencing and metabolomics. The data showed that STA improved heart function, reduced intestinal permeability, and suppressed inflammation in mice in a dose-dependent manner. However, the compound had little influence on the overall alpha diversity of gut microbiota, while it did influence the beta diversity. The analyses based on the multiomics strategy demonstrated that certain GI microbial groups, including <i>Paramuribaculum</i>, <i>Allobaculum</i>, <i>Bifidobacterium</i>, and <i>Adlercreutzia</i>, responded to the STA administration, which contributed to the alternatives of metabolites in the gut. Correlation analyses showed that <i>Duncaniella</i> and <i>Ruminococcus</i> negatively impacted health, while <i>Muribaculum</i>, <i>Paramuribaculum</i>, and <i>Prevotella</i> positively influenced intestinal permeability and heart health. Collectively, STA attenuated T2D-induced cardiac disorders by improving heart structure and function and suppressing inflammation, during which the GI homeostasis of the T2D mice changed to an alternative state that was different from that of healthy mice.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481466","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":"New Benzothiazole-Thiadiazole-Based Ketones as Potential Antiviral and Anticancer Agents: Synthesis, DFT, and Molecular Docking Studies","authors":"Khadra B. Alomari,&nbsp;Abdulmajeed F. Alrefaei,&nbsp;Renad Almughathawi,&nbsp;Nuha M. Halawani,&nbsp;Sara A. Alqarni,&nbsp;Arwa Alharbi,&nbsp;Hanadi A. Katouah,&nbsp;Nashwa M. El-Metwaly","doi":"10.1111/cbdd.70073","DOIUrl":"https://doi.org/10.1111/cbdd.70073","url":null,"abstract":"<div>\u0000 \u0000 <p>Various substituted benzothiazole-thiadiazole-based ketones <b>4a-i</b> and <b>6a-c</b> were synthesized and characterized by the IR, NMR, and MS spectral data. The DFT study of the synthesized ketones <b>4</b> and <b>6</b> displayed matched configurations of their HOMO and LUMO, with the exception of the nitrophenyl derivatives, whose HOMO extended over the entire molecule. Meanwhile, the antiproliferative effectiveness of the produced ketones was evaluated against diverse cell lines and compared with the reference drug Erlotinib. The ketones exhibited variable inhibitory effects, for example, the ketone <b>6a</b> has the most potent activity versus Panc-1 (IC₅₀ = 9.34 ± 0.18 μM), whereas <b>4i</b> showed proper effectiveness against HepG2 (IC₅₀ = 10.91 ± 0.23 μM), and ketone <b>4a</b> exhibited strong activity against MCF-7 cells (IC₅₀ = 5.66 ± 0.16 μM). Moreover, the H5N1 antiviral efficacy was assessed via a plaque reduction assay, using amantadine as a reference drug. Ketones <b>2a</b>, <b>4e</b>, and <b>4g</b> displayed 100% inhibition, while ketone <b>4e</b> has the lowest toxic concentration (TC₅₀ 61 μg/μL). Furthermore, the molecular docking results revealed that ketone <b>4e</b> had the highest binding score owing to several interactions with amino acids of 1JU6 residues. Finally, SwissADME analysis of the synthesized ketones provides key insights into their pharmacokinetic properties.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475663","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":"Design and Synthesis of Novel MEK Inhibitors for the Treatment of Solid Tumors","authors":"Jingting Zeng,&nbsp;Zhenshuo Luo,&nbsp;Tiansheng Zhao,&nbsp;Chunhua Xia,&nbsp;Fanglan Liu,&nbsp;Na Li,&nbsp;Lailiang Qu,&nbsp;Cheng Wang","doi":"10.1111/cbdd.70067","DOIUrl":"https://doi.org/10.1111/cbdd.70067","url":null,"abstract":"<div>\u0000 \u0000 <p>Aberrant activation of the RAS/RAF/MEK/ERK pathway occurs in more than 30% of human cancers. As part of this pathway, MEK1/2 has crucial roles in tumorigenesis, cell proliferation, and inhibition of apoptosis. At present, a number of MEK1/2 inhibitors are approved for the treatment of melanoma. However, MEK1/2 inhibitors have poor single-drug efficacy in the treatment of solid tumors and are prone to drug resistance. A series of compounds containing a diarylamine skeleton and phenylacrylamide (acrylamide) have been designed and synthesized in this paper. The most promising compound M15 showed good inhibitory activity of MEK1 (IC₅₀ = 10.29 nM) and good inhibitory effect on three types of solid tumor cells: MDA-MB-231(IC₅₀ = 2.76 μM), HepG2 (IC₅₀ = 2.57 μM) and A549 (IC₅₀ = 5.40 μM). At the same time, <b>M15</b> was less toxic to human normal cells (MCF-10A IC₅₀ &gt; 20 μM) and has certain stability of liver microsomes in vitro (human, <i>t</i>_1/2 = 27.9 min; rat, <i>t</i>_1/2 &gt; 60 min). It can induce apoptosis of MDA-MB-231 cells and slow down their migration. Therefore, compound <b>M15</b> acts as a novel MEK1/2 inhibitor and may be a promising candidate for solid tumor intervention.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439112","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":"99mTc-HYNIC PEGylated Peptide Probe Targeting HER2-Expression in Breast Cancer","authors":"Sushree Arpitabala Yadav,&nbsp;V. Kusum Vats,&nbsp;Sonal Gupta,&nbsp;Krishna Mohan Repaka,&nbsp;Drishty Satpati","doi":"10.1111/cbdd.70064","DOIUrl":"https://doi.org/10.1111/cbdd.70064","url":null,"abstract":"<div>\u0000 \u0000 <p>Increased HER2 expression during breast cancer and its metastatic spread can be checked by specific probes having high affinity towards the target. This study aimed at developing ^99mTc-labelled HER2-specific molecular probe for accurate detection. The two rL-A9 peptide variants, HYNIC-rL-A9 and HYNIC-PEG₁₂-rL-A9 were manually synthesized by solid phase methodology. ^99mTc-labelling of peptides was accomplished using EDDA and tricine as co-ligands. [^99mTc]Tc-HYNIC-rL-A9 showed poor uptake in HER2-expressing human breast carcinoma SKBR3 cells whereas the PEGylated counterpart [^99mTc]Tc-HYNIC-PEG₁₂-rL-A9 demonstrated high specific cellular uptake (3.01% ± 0.14%) and low nanomolar binding affinity (<i>K</i>_<i>d</i> = 17.11 ± 7.63 nM). Tumour uptake (SKBR3) of [^99mTc]Tc-HYNIC-PEG₁₂-rL-A9 was higher at 1 and 3 h in comparison to the non-PEGylated radiopeptide. Blocking studies led to 70% reduction in accumulation of radioactivity in the tumour indicating specificity of the radiopeptide. Introduction of polyethylene glycol (PEG₁₂) as pharmacokinetic modifier led to significantly improved biological profile of the [^99mTc]Tc-HYNIC-labelled rL-A9 peptide conjugate.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439111","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":"Anti-Inflammatory Compounds From Roots of Heracleum sphondylium subsp. cyclocarpum","authors":"Ekin Kurtul,&nbsp;Özlem Bahadır Acıkara,&nbsp;Büşra Karpuz Ağören,&nbsp;Esra Küpeli Akkol","doi":"10.1111/cbdd.70044","DOIUrl":"https://doi.org/10.1111/cbdd.70044","url":null,"abstract":"<p><i>Heracleum sphondylium</i> subsp. <i>cyclocarpum</i> (K. Koch) P.H. Davis from <i>Heracleum</i> L. genus, which is one of the widest genera of the Apiaceae family and known as “Hogweed or Tavşancılotu”. This genus has a variety of traditional uses, including treating gastrointestinal, cardiovascular, gynecological, and cognitive disorders, skin problems, rheumatism, and inflammation. In particular, these plants are commonly used for inflammatory diseases. This research aimed to examine in detail the anti-inflammatory properties of <i>Heracleum sphondylium</i> subsp. <i>cyclocarpum</i> roots. Bioactivity-guided fractionation was used to isolate the active compounds. Carrageenan- and prostaglandin E2-induced inflammation models were employed to test the activity. Dichloromethane and methanolic extracts of the plant material were tested for activity and found to be effective in inhibiting inflammation. The subfractions obtained by column chromatography were further evaluated for their activities. The active fractions were used to obtain responsible compounds by using semipreparative HPLC. Five coumarin derivatives were isolated and identified as heraclenol (1), byakangelicin (2), heraclenol-3″-<i>O</i>-<i>β</i>-glucoside (3), byakangelicin-3″-<i>O</i>-<i>β</i>-glucoside (4), and meranzin hydrate III (5). The isolated compounds were investigated for their anti-inflammatory activities, and heraclenol-3″-<i>O-β</i>-glucoside was found to inhibit the carrageenan and prostaglandin E2-induced edema significantly compared to the control group and have higher activity than the extracts.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Hemisynthesis, Characterization, Molecular Docking, and Dynamics Evaluation of Novel Totarol-1,2,3-Triazole Derivatives as Leishmaniasis and Toxoplasmosis Agents","authors":"Ayoub Boualli,&nbsp;Yassine Laamari,&nbsp;Abdoullah Bimoussa,&nbsp;Syeda Abida Ejaz,&nbsp;Hafiz Muhammad Attaullah,&nbsp;Abdelkhalek Riahi,&nbsp;Anthony Robert,&nbsp;Jean-Claude Daran,&nbsp;Ibrahim S. Al Nasr,&nbsp;Waleed S. Koko,&nbsp;Tariq A. Khan,&nbsp;Bernhard Biersack,&nbsp;Aziz Auhmani,&nbsp;My Youssef Ait Itto","doi":"10.1111/cbdd.70042","DOIUrl":"https://doi.org/10.1111/cbdd.70042","url":null,"abstract":"<div>\u0000 \u0000 <p>Tropical parasitic diseases like leishmaniasis pose significant public health challenges, impacting millions of individuals globally. Current drug treatments for these diseases have notable drawbacks and side effects, underscoring the pressing need for new medications with improved selectivity and reduced toxicity. Through structural modifications of both natural and synthetic compounds using click chemistry, researchers have been able to produce derivatives showing promising activity against these parasites. In this study, 21 novel 1,2,3-triazole analogues of totarol were synthesized using <i>O</i>-propargylated totarol derivatives and substituted arylazide. These compounds were characterized through various analytical techniques, including ¹H NMR, ¹³C NMR, and HRMS. An x-ray crystallographic study of compounds <b>4</b> and <b>6</b> was carried out to fully establish the structure of the newly prepared totarol derivatives. All synthesized compounds were then screened in vitro for their antileishmanial activities against <i>Leishmania major</i> promastigotes, amastigotes, and <i>Toxoplasma gondii</i> tachyzoites Out of the tested analogues, six compounds (<b>7c, 8b–e</b>, and <b>9 g</b>) displayed antileishmanial activity against <i>L. major</i> amastigotes with IC₅₀ 17.3, 14.2, 13.1 18.2 13.2 and 17.3 μg mL⁻¹ respectively, while only <b>8e</b> gave antileishmanial activity against both promastigotes and amastigotes with IC₅₀ 11.7 and 13.2 μg mL⁻¹ respectively. Additionally, the presence of a nitro group was correlated with enhanced antileishmanial activity. Moreover, a molecular docking study was conducted, focusing on <b>8e</b>, the most active antileishmanial compound, to elucidate its putative binding pattern at the active site of the selected leishmanial trypanothione reductase target.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404665","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":"Baicalein Inhibits Tumor Property of Hepatocellular Carcinoma Cells Through the Inactivation of the E2F Transcription Factor 1/Mediator Complex Subunit 7 Axis","authors":"Pinghui Song,&nbsp;Naiying Shen,&nbsp;Zhongkun Wu,&nbsp;Sha He","doi":"10.1111/cbdd.70063","DOIUrl":"https://doi.org/10.1111/cbdd.70063","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with poor prognosis. Baicalein, a natural compound, can regulate multiple cellular processes in various cancer types. In this study, we investigated the role of baicalein in regulating HCC and explored its potential mechanism. The expression of mediator complex subunit 7 (MED7) and E2F transcription factor 1 (E2F1) was analyzed by quantitative real-time polymerase chain reaction or Western blotting assay. Cell proliferation was assessed by cell colony formation assay and 5-ethynyl-2′-deoxyuridine assay. Cell migration was analyzed by transwell assay and wound-healing assay. Cell invasion was analyzed by transwell assay. Angiogenic ability of HCC cells was assessed by tube formation assay. Dual-luciferase reporter assay and chromatin immunoprecipitation assay were performed to validate the association between E2F1 and MED7. The xenograft mouse model assay was conducted to determine the effects of baicalein and E2F1 overexpression on tumor formation. Immunohistochemistry assay was used to determine positive expression rates of proteins. Upregulation of MED7 and E2F1 expression was observed in both HCC tissues and cells. Knockdown of MED7 suppressed HCC cell proliferation, migration, invasion, and tube formation. Transcriptional activation of MED7 by E2F1 was demonstrated in HCC cells. Overexpression of MED7 mitigated the effects induced by E2F1 depletion in HCC cells. Additionally, baicalein treatment effectively inhibited the tumor property of HCC cells by decreasing E2F1 expression in both in vitro and in vivo models. Baicalein inhibited the tumor property of HCC cells through the inactivation of the E2F1/MED7 axis, highlighting its potential clinical application in the treatment of HCC.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388901","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":"Potential Modulatory Effects of Hesperidin on the JAK/STAT Pathway in Mesangial Proliferative Glomerulonephritis","authors":"Yingchun Tang,&nbsp;Jing Zhang,&nbsp;Zhengxiang Wang,&nbsp;Xiongjun Dong","doi":"10.1111/cbdd.70032","DOIUrl":"https://doi.org/10.1111/cbdd.70032","url":null,"abstract":"<div>\u0000 \u0000 <p>Mesangial proliferative glomerulonephritis (MsPGN) is a common type of glomerular disease characterized by immune complex deposition and inflammation in the kidney, leading to renal dysfunction. Currently, treatment options for MsPGN are limited, and there is a need for effective therapeutic interventions. Hesperidin (HSP), a natural flavonoid glycoside, has shown promising anti-inflammatory and antioxidant properties in various disease models. This study aimed to investigate the therapeutic potential of HSP for MsPGN and explore its possible mechanism of action. A male Wistar rat model of MsPGN was established via tail vein injection of Thy-1 monoclonal antibody, and the rats were divided into four groups: Control, MsPGN, MsPGN + HSP, and MsPGN + Prednisone. After 7 days of intervention, the therapeutic effects of HSP were evaluated through biochemical and histological analyses. Our results demonstrated that HSP treatment significantly reduced the levels of blood urea nitrogen, serum creatinine, total cholesterol, and triglycerides, and improved renal pathology. Additionally, pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, interleukin-2, and monocyte chemoattractant protein-1, were markedly decreased. Immunofluorescence analysis revealed reduced levels of immunoglobulin G and C5b-9, along with decreased immune complex deposition in the kidneys. Furthermore, HSP downregulated the phosphorylation levels of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), suggesting modulation of the JAK/STAT pathway. In conclusion, HSP might effectively alleviate renal injury, reduce renal inflammatory response, and inhibit renal immune complex deposition, potentially through the suppression of the JAK/STAT pathway.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380715","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":"Analyzing Oxygen Atom Distribution in FDA-Approved Drugs to Enhance Drug Discovery Strategies","authors":"Vijay H. Masand,&nbsp;Meghshyam K. Patil,&nbsp;Sami A. Al-Hussain,&nbsp;Abdul Samad,&nbsp;Vesna Rastija,&nbsp;Rahul D. Jawarkar,&nbsp;Gaurav S. Masand,&nbsp;Rakhi G. Gawali,&nbsp;Magdi E. A. Zaki","doi":"10.1111/cbdd.70060","DOIUrl":"https://doi.org/10.1111/cbdd.70060","url":null,"abstract":"<div>\u0000 \u0000 <p>Despite advancements in molecular design rules and understanding biochemical processes, the field of drug design and discovery seeks to minimize the number and duration of synthesis-testing cycles to convert lead compounds into drug candidates. A promising strategy involves gaining insightful understanding of key heteroatoms such as oxygen and nitrogen. This work presents a comprehensive analysis of oxygen atoms in approved drugs, aiming to streamline drug design and discovery efforts. The study examines the frequency, distribution, prevalence, and diversity of oxygen atoms in a dataset of 2049 small molecules approved by the FDA and other agencies. The analysis focuses on various types of oxygen atoms, including sp³, sp²-hybridized, ring, and nonring. In general, existence of sp³-O slightly outperforms sp²-O, which is associated with balancing various factors such as flexibility, solubility, stability, and pharmacokinetics, in addition to activity and selectivity. In approved drugs, majority of oxygen atoms are present within 4 Å from the COM of the molecule. This analysis offers valuable understanding of oxygen distribution, which could be used during the multiparameter optimization process, facilitating the transformation of a hit/lead compound into a potential drug candidate.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248762","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}