Molecular Diversity最新文献

{"title":"Curcumin interferes with chitin synthesis in Aedes aegypti: a computational and experimental investigation","authors":"Priyashi Rao,&nbsp;Jinal Ninama,&nbsp;Mansi Dudhat,&nbsp;Dweipayan Goswami,&nbsp;Rakesh M. Rawal","doi":"10.1007/s11030-023-10672-0","DOIUrl":"10.1007/s11030-023-10672-0","url":null,"abstract":"<div><p>Throughout history, vector-borne diseases have consistently posed significant challenges to human health. Among the strategies for vector control, chemical insecticides have seen widespread use since their inception. Nevertheless, their effectiveness is continually undermined by the steady growth of insecticide resistance within these vector populations. As such, the demand for more robust, efficient, and cost-effective natural insecticides has become increasingly pressing. One promising avenue of research focuses on chitin, a crucial structural component of mosquitoes' exoskeletons and other insects. Chitin not only provides protection and rigidity but also lends flexibility to the insect body. It undergoes substantial transformations during insect molting, a process known as ecdysis. Crucially, the production of chitin is facilitated by an enzyme known as chitin synthase, making it an attractive target for potential novel insecticides. Our recent study delved into the impacts of curcumin, a natural derivative of turmeric, on chitin synthesis and larval development in <i>Aedes aegypti</i>, a mosquito species known to transmit dengue and yellow fever. Our findings demonstrate that even sub-lethal amounts of curcumin can significantly reduce overall chitin content and disrupt the cuticle development in the 4th instar larvae of <i>Aedes aegypti</i>. Further to this, we utilized computational analyses to investigate how curcumin interacts with chitin synthase. Techniques such as molecular docking, pharmacophore feature mapping, and molecular dynamics (MD) simulations helped to illustrate that curcumin binds to the same site as polyoxin D, a recognized inhibitor of chitin synthase. These findings point to curcumin's potential as a natural, bioactive larvicide that targets chitin synthase in mosquitoes and potentially other insects.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":"28 3","pages":"1505 - 1529"},"PeriodicalIF":3.9,"publicationDate":"2023-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9683877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of phytochemical inhibitors targeting phosphate acetyltransferase of Mycoplasma genitalium: insights from virtual screening and molecular dynamics studies","authors":"Krishnendu Barik,&nbsp;Praffulla Kumar Arya,&nbsp;Ajay Kumar Singh,&nbsp;Anil Kumar","doi":"10.1007/s11030-023-10681-z","DOIUrl":"10.1007/s11030-023-10681-z","url":null,"abstract":"<div><p><i>Mycoplasma genitalium</i> (<i>M. genitalium</i>) has evolved as a superbug, and the developing antimicrobial resistance with just a few treatment options available is an imminent concern. Due to the emergence of antibiotic resistance, a new antibiotic class or medications are required to combat this pathogen. The phosphate acetyltransferase (PTA) enzyme can be a suitable drug target which is essential for <i>M. genitalium</i> survival and involves in acetate metabolism. To efficiently find potent inhibitors, structure-based drug design approaches targeting the PTA of <i>M. genitalium</i> have been established. In this study, the three most potent phytochemical inhibitors were predicted from virtual screening and these are sitostanyl ferulate, beta-sitosterol-beta-<span>d</span>-glucoside, and brassinolide, with binding energies of − 9.66, − 9.60, and − 9.48 kcal/mol, respectively. The active site residues Thr-125, Arg-300, Ser-299, Tyr-272, and Lys-273 appear to be critical in binding the three predicted potent inhibitors. The results of the molecular dynamics study indicate that the three predicted phytochemical inhibitors have formed stable bonds with PTA. Molecular Mechanics Poisson–Boltzmann Surface Area (MM-PBSA) was utilized for the estimation of binding free energy of PTA-phytochemical complexes. Taken together, the findings of our computational work might aid in the development of possible potential drugs to treat and ameliorate the severity of <i>M. genitalium</i> infection.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":"28 3","pages":"1651 - 1663"},"PeriodicalIF":3.9,"publicationDate":"2023-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10035846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extraction, isolation, synthesis, and biological evaluation of novel piperic acid derivatives for the treatment of Alzheimer’s disease","authors":"Jitendra Kumar,&nbsp;Gauri Shankar,&nbsp;Sunil Kumar,&nbsp;Jobin Thomas,&nbsp;Neha Singh,&nbsp;Saripella Srikrishna,&nbsp;Jitendra Satija,&nbsp;Sairam Krishnamurthy,&nbsp;Gyan Modi,&nbsp;Sunil Kumar Mishra","doi":"10.1007/s11030-023-10667-x","DOIUrl":"10.1007/s11030-023-10667-x","url":null,"abstract":"<div><p>In this paper, we developed a series of piperic acid (<b>PA</b>) analogs with the aim of overcoming the limitations associated with the natural products for the management of Alzheimer’s disease (AD). A comprehensive SAR study was performed to enhance cholinesterase inhibition of <b>PA</b>. The acetylcholinesterase inhibition and its kinetic data suggested <b>6j</b> as the lead molecule (AChE IC₅₀ = 2.13 ± 0.015<i> µM</i>, BChE = 28.19 ± 0.20%), in comparison to <b>PA</b> (AChE = 7.14 ± 0.98%) which was further selected for various biological studies in AD models. <b>6j</b>, exhibited interaction with the peripheral anionic site of AChE, BBB permeability (<i>Pe</i> = 7.98), and antioxidant property (% radical scavenging activity = 35.41 ± 1.09, 2.43 ± 1.65, for <b>6j</b> and <b>PA</b> at 20 M<span>(mu )</span>, respectively). The result from the metal chelation study suggests that <b>6j</b> did not effectively chelate iron. The molecular modeling studies suggested that <b>6j</b> could effectively interact with Ser293, Phe295, Arg296, and Tyr34 of AChE. In the cell-based cytotoxicity studies, <b>6j</b> exhibited cytocompatibility at the different tested concentrations. The acute toxicity data on mice suggested that compound <b>6j</b> had no renal and hepatotoxicity at 500 mg/kg. Moreover, <b>6j</b> could effectively reverse scopolamine-induced amnesia by improving spatial and cognitive memory in mice. The above results strongly suggest that compound <b>6j</b> may act as a novel multi-targeted lead for AD therapy.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":"28 3","pages":"1439 - 1458"},"PeriodicalIF":3.9,"publicationDate":"2023-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9675098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and synthesis of pyrrolo[2,3-d]pyrimidine linked hybrids as α-amylase inhibitors: molecular docking, MD simulation, ADMET and antidiabetic screening","authors":"Ajayrajsinh R. Zala,&nbsp;Ramgopal Tiwari,&nbsp;Hem N. Naik,&nbsp;Iqrar Ahmad,&nbsp;Harun Patel,&nbsp;Smita Jauhari,&nbsp;Premlata Kumari","doi":"10.1007/s11030-023-10683-x","DOIUrl":"10.1007/s11030-023-10683-x","url":null,"abstract":"<div><p>Novel pyrrolo[2,3-<i>d</i>]pyrimidine-based analogues were designed, synthesized, and evaluated for their ability to inhibit the α-amylase enzyme in order to treat diabetes. In vitro antidiabetic analysis demonstrated excellent antidiabetic action for compounds <b>5b, 6c, 7a,</b> and <b>7b,</b> with IC₅₀ values in the <b>0.252–0.281 mM</b> range. At a 200 μg/mL concentration, the exceptional percent inhibition values for compounds <b>5a, 5b, 5d,</b> and <b>6a</b> varied from <b>97.79 ± 2.86%</b> to <b>85.56 ± 4.13%</b> overperforming the standard (acarbose). Molecular docking of all compounds performed with <i>Bacillus paralicheniformis</i> α-amylase enzyme. The most active compounds via in vitro and non-toxic via in silico ADMET and molecular docking analysis, hybrids <b>6c, 7a,</b> and <b>7b</b> displayed binding affinity from <b>− 8.2</b> and <b>− 8.5 kcal/mol</b>. Molecular dynamic simulations of most active compound <b>5b</b> and <b>7a</b> investigated into the active sites of the <i>Bacillus paralicheniformis</i> α-amylase enzyme for a 100-ns indicating the stability of hybrid-protein complex. Consistent RGyr values for the two complexes under study further suggest that the system's proteins are closely packed in the dynamic state. Synthesized analogs’ in vitro biological assessments, ADMET, molecular docking, and MD modelling reveal that <b>5b, 6c, 7a,</b> and <b>7b</b> hybrid analogs may be employed in the development of future antidiabetic drugs.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":"28 3","pages":"1681 - 1695"},"PeriodicalIF":3.9,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9674113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of potential inhibitors of cholinergic and β-secretase enzymes from phytochemicals derived from Gongronema latifolium Benth leaf: an integrated computational analysis","authors":"Gideon Ampoma Gyebi,&nbsp;Oludare M. Ogunyemi,&nbsp;Ibrahim M. Ibrahim,&nbsp;Olalekan B. Ogunro,&nbsp;Saheed O. Afolabi,&nbsp;Rotimi J. Ojo,&nbsp;Gabriel O. Anyanwu,&nbsp;Gaber El-Saber Batiha,&nbsp;Joseph O. Adebayo","doi":"10.1007/s11030-023-10658-y","DOIUrl":"10.1007/s11030-023-10658-y","url":null,"abstract":"<div><p>Neurodegenerative disorders (NDDs) are associated with increased activities of the brain acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and β-secretase enzyme (BACE1). Inhibition of these enzymes affords therapeutic option for managing NDDs such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Although, <i>Gongronema latifolium</i> Benth (GL) has been widely documented in ethnopharmacological and scientific reports for the management of NDDs, there is paucity of information on its underlying mechanism and neurotherapeutic constituents. Herein, 152 previously reported <i>Gongronema latifolium</i> derived-phytochemicals (GLDP) were screened against <i>h</i>AChE, <i>h</i>BChE and <i>h</i>BACE-1 using molecular docking, molecular dynamics (MD) simulations, free energy of binding calculations and cluster analysis. The result of the computational analysis identified silymarin, alpha-amyrin and teraxeron with the highest binding energies (-12.3, -11.2, -10.5 Kcal/mol) for <i>h</i>AChE, <i>h</i>BChE and <i>h</i>BACE-1 respectively as compared with those of the reference inhibitors (-12.3, -9.8 and − 9.4 for donepezil, propidium and aminoquinoline compound respectively). These best docked phytochemicals were found to be orientated in the hydrophobic gorge where they interacted with the choline-binding pocket in the A-site and P-site of the cholinesterase and subsites S1, S3, S3’ and flip (67–75) residues of the pocket of the BACE-1. The best docked phytochemicals complexed with the target proteins were stable in a 100 ns molecular dynamic simulation. The interactions with the catalytic residues were preserved during the simulation as observed from the MMGBSA decomposition and cluster analyses. The presence of these phytocompounds most notably silymarin, which demonstrated dual high binding tendencies to both cholinesterases, were identified as potential neurotherapeutics subject to further investigation.</p></div>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":"28 3","pages":"1305 - 1322"},"PeriodicalIF":3.9,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10037598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular docking and simulation studies of some pyrazolone-based bioactive ligands targeting the NF-(kappa)B signaling pathways","authors":"Surya Philip,&nbsp;D. R. Sherin,&nbsp;T. K. Manoj Kumar,&nbsp;T. C. Badisha Banu,&nbsp;Reny Mary Roy","doi":"10.1007/s11030-023-10668-w","DOIUrl":"10.1007/s11030-023-10668-w","url":null,"abstract":"<div><p>NF-κB has become a predominant regulator responsible for multiple physiological and pathological processes. NF-κB signaling pathway has canonical and non-canonical components which strategize the cancer-related metabolic processes. Non-canonical NF-κB pathways are known to contribute towards the chemoresistance of cancer cells. Consequently, NF-κB can be utilized as a potential therapeutic target for modifying the behaviour of tumor cells. In view of this, we herein report a series of pyrazolone-based bioactive ligands that potentially target NF- κB and, thereby, unveil their anticancer properties. The pharmacological screening of the synthesized compounds were carried out using various virtual screening techniques. The anticancer studies of synthesized pyrazolones showed that APAU exhibited the most potent effect against the MCF-7 cells with an IC₅₀ value of 30 μg/ml. Molecular docking studies revealed that the pyrazolones inhibited cell proliferation by targeting the NFκB signaling pathway. The molecular dynamics simulation studies predicted the stability and flexibility of pyrazolone-based bioactive ligands.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":"28 3","pages":"1459 - 1469"},"PeriodicalIF":3.9,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10037599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regioselective synthesis and molecular docking studies of functionalized imidazo [1,2-a]pyridine derivatives through MCRs","authors":"Maruti B. Yadav,&nbsp;Pooja Singh,&nbsp;Yeon Tae Jeong","doi":"10.1007/s11030-023-10669-9","DOIUrl":"10.1007/s11030-023-10669-9","url":null,"abstract":"<div><p>\u0000A efficient protocol has been developed for the synthesis of regioselective imidazo[1,2-<i>a</i>]pyridine and imidazo[1,2-<i>a</i>]pyrimidine derivatives through cascade reaction between 2-aminopyridine, arylelglyoxal, and 4-hydroxypyran via three-component reaction to prepare targeted compounds with good to excellent yields. The advantages of this transformation are a catalyst-free reaction, green solvent, operationally simple, scalable, and eco-friendly. The product collects with simple filtration which avoided tedious and expensive purification techniques. In addition, computational studies like molecular docking were conducted to provide the theoretical possibilities of binding these types of synthesized compounds to the VEGFR2 receptors as potential key inhibitors of tumor cell growth and angiogenesis.</p></div>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":"28 1","pages":"171 - 182"},"PeriodicalIF":3.9,"publicationDate":"2023-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9662996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, antidiabetic activity and molecular docking studies of novel aryl benzylidenethiazolidine-2,4-dione based 1,2,3-triazoles","authors":"Nagesh Patnam,&nbsp;Kishan Chevula,&nbsp;Prasad Chennamsetti,&nbsp;Balaswamy Aleti,&nbsp;Aruna Kumari Kotha,&nbsp;Vijjulatha Manga","doi":"10.1007/s11030-023-10674-y","DOIUrl":"10.1007/s11030-023-10674-y","url":null,"abstract":"<p>A series of novel aryl benzylidenethiazolidine-2,4-dione based 1,2,3-triazoles synthesized in a straightforward route consisting of benzylidenethiazolidine-2,4-dione and 1,2,3-triazole pharmacophores. The new scaffolds tested for in vitro antidiabetic activity by inhibition of aldose reductase enzyme and its inhibition measured in half of Inhibition Concentration (IC₅₀). The activity results correlated with standard reference <i>Sorbinil</i> (IC₅₀: 3.45 ± 0.25 µM). Among all the titled compounds <b>8f</b> (1.42 ± 0.21 µM), <b>8d</b> (1.85 ± 0.39 µM), <b>13a</b> (1.94 ± 0.27 µM) and <b>8b</b> (1.98 ± 0.58 µM) shown potent activity. In addition, molecular docking results against the crystal structure of aldose reductase (PDB ID: 1PWM) revealed that the binding affinities shown by all synthesized compounds are higher than the reference compound <i>Sorbinil.</i> The docking scores, H-bond interactions, and hydrophobic interactions well defined inhibition strength of all compounds.\u0000</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":"28 3","pages":"1551 - 1563"},"PeriodicalIF":3.9,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9643421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chrysin based pyrimidine-piperazine hybrids: design, synthesis, in vitro antimicrobial and in silico E. coli topoisomerase II DNA gyrase efficacy","authors":"Kajalben B. Patel,&nbsp;Dhanji Rajani,&nbsp;Iqrar Ahmad,&nbsp;Harun Patel,&nbsp;Hitesh D. Patel,&nbsp;Premlata Kumari","doi":"10.1007/s11030-023-10663-1","DOIUrl":"10.1007/s11030-023-10663-1","url":null,"abstract":"<div><p>Ten chrysin-based pyrimidine-piperazine hybrids have been evaluated in vitro for antimicrobial activity against eleven bacterial and two fungal strains. All compounds <b>5a–j</b> exhibited moderate to good inhibition, with MIC values ranging from 6.25 to 250 µg/ml. At 6.25 µg/ml and 12.5 µg/ml MIC values, respectively, compounds <b>5b</b> and <b>5h</b> demonstrated the most promising potency against <i>E. coli,</i> outperforming ampicillin, chloramphenicol, and ciprofloxacin. None of the substances had the same level of action as norfloxacin. <b>5a, 5d, 5g, 5h, and 5i</b> have exhibited superior antifungal efficacy than Griseofulvin against <i>C. albicans</i> with 250 µg/ml MIC. All the compounds were also individually docked into the <i>E. coli</i> DNA gyrase ATP binding site (PDB ID: 1KZN) and CYP51 inhibitor (PDB ID: 5V5Z). The most active compound, <b>5h</b> and <b>5g</b> displayed a Glide docking score of − 5.97 kcal/mol and − 10.99 kcal/mol against DNA gyrase and 14α-demethylase enzyme CYP51 respectively. Potent compounds <b>5b, 5h,</b> and <b>5g</b> may be used to design new, innovative antimicrobial agents, according to in vitro, ADMET, and in silico biological efficacy analyses.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":"28 3","pages":"1377 - 1392"},"PeriodicalIF":3.9,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10005918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of bis-thiohydantoin derivatives as an antiproliferative agents targeting EGFR inhibitory pathway","authors":"Alaa A. Hassan,&nbsp;Ashraf A. Aly,&nbsp;Mohamed Ramadan,&nbsp;Nasr K. Mohamed,&nbsp;Bahaa G. M. Youssif,&nbsp;Hesham A. M. Gomaa,&nbsp;Stefan Bräse,&nbsp;Martin Nieger,&nbsp;Amal S. Abd El-Aal","doi":"10.1007/s11030-023-10653-3","DOIUrl":"10.1007/s11030-023-10653-3","url":null,"abstract":"<div><p>(<i>R</i>)/(<i>S</i>)-the two enantiomers of 3-substituted-1-[2-(5)-3-substituted-4-benzyl-5-oxo-4-phenyl-2-thioxoimid-azolidin-1-yl]ethyl/propyl-5-benzyl-5-phenyl-2-thioxoimidazolidin-4-ones were formed during the diastereoselective reaction between <i>N</i>,<i>N″</i>-1,ω-alkanediylbis[<i>N′-</i>organylthiourea] derivatives and 2,3-diphenylcyclopropenone in refluxing ethanol. The structures of the isolated compounds were confirmed by NMR, IR, mass spectra and elemental analyses. Moreover, single-crystal X-ray structure analysis was also used to elucidate the structure of the isolated compounds. The mechanism describes the reaction was also discussed. The tested compounds showed EGFR inhibitory activity with IC₅₀ values ranging from 90 to 178 nM in comparison to the erlotinib as a reference with IC₅₀ value of 70 nM. Compound <b>4c</b> (R = allyl, n = 3) was found as the most potent antiproliferative, had the highest inhibitory effect on EGFR with an IC₅₀ value of 90 nM, compared to erlotinib’s IC₅₀ value of 70 nM. The second and third-most active compounds were <b>4e</b> (R = phenyl, n = 3) and <b>4d</b> (R = ethyl, n = 3) and with IC₅₀ values of 107 nM and 128 nM. These findings imply that the compounds tested had a significant antiproliferative effect as well as the ability to act as an EGFR inhibitor. Docking studies showed that compound <b>4c</b> showed high affinity to EGFR based on its docking score (S; kcal/mol) within five test compounds.\u0000</p></div>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":"28 3","pages":"1249 - 1260"},"PeriodicalIF":3.9,"publicationDate":"2023-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9668475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}