{"title":"作为 MDM2-p53 抑制剂的螺吲哚衍生物的合成、晶体结构、Hirshfeld 表面、计算和生物学研究。","authors":"Monisha Sivanandhan, Sutha Ragupathy, Arumugam Thangamani, Amutha Parasuraman","doi":"10.1007/s11030-024-10974-x","DOIUrl":null,"url":null,"abstract":"<p><p>The spiro-oxindole derivatives were synthesized via a 1,3-dipolar cycloaddition approach and characterized by FT-IR, <sup>1</sup>H, <sup>13</sup>C NMR and mass spectral techniques. The single crystal XRD of 6d further validates the formation of compounds. DFT calculations indicated the reactive nature of compound 6d. Docking studies with 5LAW disclosed the minimum binding energy of - 10.83 kcal/mol for 6d. Furthermore, safe oral bioavailability was ensured by the physicochemical, pharmacokinetic, and toxicity predictions. The anticancer analysis of synthesized compounds showed substantial activity against A549 cells, notably with an IC<sub>50</sub> value of 8.13 ± 0.66 µM for 6d compared to standard doxorubicin. 6d was also evaluated for cytotoxicity against L929 healthy cells and A549, showing selectivity towards A549 than healthy cells. AO/EB staining method showed early apoptotic cellular death in the A549 cell line in a dose-dependent manner.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis, crystal structure, Hirshfeld surface, computational and biological studies of spiro-oxindole derivatives as MDM2-p53 inhibitors.\",\"authors\":\"Monisha Sivanandhan, Sutha Ragupathy, Arumugam Thangamani, Amutha Parasuraman\",\"doi\":\"10.1007/s11030-024-10974-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The spiro-oxindole derivatives were synthesized via a 1,3-dipolar cycloaddition approach and characterized by FT-IR, <sup>1</sup>H, <sup>13</sup>C NMR and mass spectral techniques. The single crystal XRD of 6d further validates the formation of compounds. DFT calculations indicated the reactive nature of compound 6d. Docking studies with 5LAW disclosed the minimum binding energy of - 10.83 kcal/mol for 6d. Furthermore, safe oral bioavailability was ensured by the physicochemical, pharmacokinetic, and toxicity predictions. The anticancer analysis of synthesized compounds showed substantial activity against A549 cells, notably with an IC<sub>50</sub> value of 8.13 ± 0.66 µM for 6d compared to standard doxorubicin. 6d was also evaluated for cytotoxicity against L929 healthy cells and A549, showing selectivity towards A549 than healthy cells. AO/EB staining method showed early apoptotic cellular death in the A549 cell line in a dose-dependent manner.</p>\",\"PeriodicalId\":708,\"journal\":{\"name\":\"Molecular Diversity\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-08-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Diversity\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1007/s11030-024-10974-x\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, APPLIED\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Diversity","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1007/s11030-024-10974-x","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
Synthesis, crystal structure, Hirshfeld surface, computational and biological studies of spiro-oxindole derivatives as MDM2-p53 inhibitors.
The spiro-oxindole derivatives were synthesized via a 1,3-dipolar cycloaddition approach and characterized by FT-IR, 1H, 13C NMR and mass spectral techniques. The single crystal XRD of 6d further validates the formation of compounds. DFT calculations indicated the reactive nature of compound 6d. Docking studies with 5LAW disclosed the minimum binding energy of - 10.83 kcal/mol for 6d. Furthermore, safe oral bioavailability was ensured by the physicochemical, pharmacokinetic, and toxicity predictions. The anticancer analysis of synthesized compounds showed substantial activity against A549 cells, notably with an IC50 value of 8.13 ± 0.66 µM for 6d compared to standard doxorubicin. 6d was also evaluated for cytotoxicity against L929 healthy cells and A549, showing selectivity towards A549 than healthy cells. AO/EB staining method showed early apoptotic cellular death in the A549 cell line in a dose-dependent manner.
期刊介绍:
Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including:
combinatorial chemistry and parallel synthesis;
small molecule libraries;
microwave synthesis;
flow synthesis;
fluorous synthesis;
diversity oriented synthesis (DOS);
nanoreactors;
click chemistry;
multiplex technologies;
fragment- and ligand-based design;
structure/function/SAR;
computational chemistry and molecular design;
chemoinformatics;
screening techniques and screening interfaces;
analytical and purification methods;
robotics, automation and miniaturization;
targeted libraries;
display libraries;
peptides and peptoids;
proteins;
oligonucleotides;
carbohydrates;
natural diversity;
new methods of library formulation and deconvolution;
directed evolution, origin of life and recombination;
search techniques, landscapes, random chemistry and more;