Pub Date : 2025-08-18DOI: 10.1080/00397911.2025.2546610
Nkwane D. Thobejane (Writing – original draft) , Comfort M. Nkambule (Supervision Writing – review & editing)
An efficient synthesis of N-benzyl-3-hydroxypyrrolidines was achieved by the cyclodehydration of 4-amino-1,2-butanediols using thionyl chloride (SOCl2). The 4-amino-1,2-butanediols are readily accessible from aldehydes and ketones via homoallylic amines. While the cyclodehydration is non-stereoselective, the diastereomers are easily separated by column chromatography and the N-benzyl-3-pyrrolidinol enantiomers obtainable via Aspergillus Oryzae catalyzed transesterification.
{"title":"A simple synthesis of substituted N-benzyl-3-pyrrolidinols","authors":"Nkwane D. Thobejane (Writing – original draft) , Comfort M. Nkambule (Supervision Writing – review & editing)","doi":"10.1080/00397911.2025.2546610","DOIUrl":"10.1080/00397911.2025.2546610","url":null,"abstract":"<div><div>An efficient synthesis of <em>N</em>-benzyl-3-hydroxypyrrolidines was achieved by the cyclodehydration of 4-amino-1,2-butanediols using thionyl chloride (SOCl<sub>2</sub>). The 4-amino-1,2-butanediols are readily accessible from aldehydes and ketones via homoallylic amines. While the cyclodehydration is non-stereoselective, the diastereomers are easily separated by column chromatography and the <em>N</em>-benzyl-3-pyrrolidinol enantiomers obtainable via <em>Aspergillus Oryzae</em> catalyzed transesterification.</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"55 16","pages":"Pages 1265-1279"},"PeriodicalIF":1.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-18DOI: 10.1080/00397911.2025.2503341
Hafiza Noor Fatima (Data curation Investigation Software Writing – original draft) , Matloob Ahmad (Conceptualization Resources Supervision Writing – review & editing) , Muhammad Shahid Nazir (Data curation Methodology Visualization) , Sumayya Akram (Formal analysis Investigation Visualization) , Sana Aslam (Conceptualization Writing – original draft Writing – review & editing)
Heterocyclic chemistry has appeared as a significant part of organic chemistry due to their distinct physiological characteristics. Many biologically active nitrogen-containing heterocyclic compounds are found as a main backbone in structures of the complex compounds. Pyrrolidine is a saturated five-membered heterocyclic moiety containing secondary amine in its ring structure. Pyrrolidine derivatives occur in many plants as natural alkaloids. Pyrrolidine derivatives exhibit diverse biological activities, including anti-bacterial, anti-cancer, anti-diabetic, anti-fungal, and acetylcholinesterase (AChE) inhibitory activities. Over the past years many bioactive compounds bearing pyrrolidine moiety have been synthesized through cycloaddition reactions by using azomethine ylide and isatin as the primary reactants. Because of its multiple uses, many researchers are in efforts to produce pyrrolidine derivatives via different ways, which are helpful in therapeutics. The aim of this review is to critically discuss the synthesis of pyrrolidine and their derivatives via multicomponent approach by using different processes like ultrasound irradiation, microwave heating, catalyst-based reactions, catalyst-free, salts and azomethine ylide formation during the years 2018–2024.
{"title":"Recent synthetic methodologies for pyrrolidine derivatives through multicomponent reactions","authors":"Hafiza Noor Fatima (Data curation Investigation Software Writing – original draft) , Matloob Ahmad (Conceptualization Resources Supervision Writing – review & editing) , Muhammad Shahid Nazir (Data curation Methodology Visualization) , Sumayya Akram (Formal analysis Investigation Visualization) , Sana Aslam (Conceptualization Writing – original draft Writing – review & editing)","doi":"10.1080/00397911.2025.2503341","DOIUrl":"10.1080/00397911.2025.2503341","url":null,"abstract":"<div><div>Heterocyclic chemistry has appeared as a significant part of organic chemistry due to their distinct physiological characteristics. Many biologically active nitrogen-containing heterocyclic compounds are found as a main backbone in structures of the complex compounds. Pyrrolidine is a saturated five-membered heterocyclic moiety containing secondary amine in its ring structure. Pyrrolidine derivatives occur in many plants as natural alkaloids. Pyrrolidine derivatives exhibit diverse biological activities, including anti-bacterial, anti-cancer, anti-diabetic, anti-fungal, and acetylcholinesterase (AChE) inhibitory activities. Over the past years many bioactive compounds bearing pyrrolidine moiety have been synthesized through cycloaddition reactions by using azomethine ylide and isatin as the primary reactants. Because of its multiple uses, many researchers are in efforts to produce pyrrolidine derivatives <em>via</em> different ways, which are helpful in therapeutics. The aim of this review is to critically discuss the synthesis of pyrrolidine and their derivatives <em>via</em> multicomponent approach by using different processes like ultrasound irradiation, microwave heating, catalyst-based reactions, catalyst-free, salts and azomethine ylide formation during the years 2018–2024.</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"55 16","pages":"Pages 1201-1227"},"PeriodicalIF":1.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-18DOI: 10.1080/00397911.2025.2541185
Amol R. Shelar (Methodology) , Kisan M. Gadave (Resources Supervision Validation) , Ramdas A. Pawar (Supervision Validation) , Madhuri S. Pansare (Methodology) , Ajit P. Ingale (Investigation Methodology Supervision Writing – original draft Writing – review & editing)
A straightforward, one-pot, solvent-free, and environmentally friendly method for synthesizing 4,6-Diarylpyrimidin-2(1H)-ones through a Biginelli-type reaction is presented, utilizing sulfated tungstate as a catalyst. This approach offers enhanced product yields while employing a cost-effective and easily accessible catalyst. The simplicity of the experimental setup makes it an effective and stress-free strategy for producing 4,6-diarylpyrimidin-2-(1H)-ones. The catalyst demonstrates remarkable activity and can be reused, further contributing to the method’s efficiency.
{"title":"Sulfated tungstate: an eco-friendly and reusable catalyst for efficient one-pot synthesis of 4,6-diarylpyrimidin-2(1H)-ones in solvent-free conditions","authors":"Amol R. Shelar (Methodology) , Kisan M. Gadave (Resources Supervision Validation) , Ramdas A. Pawar (Supervision Validation) , Madhuri S. Pansare (Methodology) , Ajit P. Ingale (Investigation Methodology Supervision Writing – original draft Writing – review & editing)","doi":"10.1080/00397911.2025.2541185","DOIUrl":"10.1080/00397911.2025.2541185","url":null,"abstract":"<div><div>A straightforward, one-pot, solvent-free, and environmentally friendly method for synthesizing 4,6-Diarylpyrimidin-2(1<em>H</em>)-ones through a Biginelli-type reaction is presented, utilizing sulfated tungstate as a catalyst. This approach offers enhanced product yields while employing a cost-effective and easily accessible catalyst. The simplicity of the experimental setup makes it an effective and stress-free strategy for producing 4,6-diarylpyrimidin-2-(1<em>H</em>)-ones. The catalyst demonstrates remarkable activity and can be reused, further contributing to the method’s efficiency.</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"55 16","pages":"Pages 1247-1256"},"PeriodicalIF":1.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this study, 2-amino-5-(4-chlorophenyl)furan/thiophene were synthesized via Paal-Knorr and Gewald cyclization strategies. A series of novel furan/thiophene selenocyanate derivatives were constructed by introducing selenocyanate groups with varying chain lengths through amide bonds. All compounds were structurally characterized using NMR and HR-MS analyses. MTT assay for antitumor activity revealed that several compounds exhibited superior efficacy compared to cisplatin. Notably, furan selenocyanate 5c showed significant inhibitory activity against HepG-2 cells (IC50 = 8.64 ± 0.94 μM), while thiophene selenocyanate 11d demonstrated remarkable inhibition against HeLa and MCF-7 cells with IC50 values of 6.39 and 6.77 μM, respectively. Structure-activity relationship (SAR) analysis indicated that the carbon chain length significantly influenced antitumor activity, with the C8-chain thiophene selenocyanate derivative 11d exhibiting optimal selectivity for HeLa and MCF-7 cells. This study provides important references for development of novel selenium-containing antitumor drugs.
{"title":"Synthesis and antitumor activity of selenocyanate derivatives based on 2-amino-5-(4-chlorophenyl)furan/thiophene scaffolds","authors":"Maixia Liu (Data curation Formal analysis Investigation Methodology) , Lijie Che (Methodology Resources Validation) , Xiyan Tang (Investigation Supervision) , Chunfang Gan (Data curation Software) , Yanmin Huang (Funding acquisition Project administration Writing – review & editing) , Zhiping Liu (Investigation Supervision Writing – original draft Writing – review & editing)","doi":"10.1080/00397911.2025.2545850","DOIUrl":"10.1080/00397911.2025.2545850","url":null,"abstract":"<div><div>In this study, 2-amino-5-(4-chlorophenyl)furan/thiophene were synthesized <em>via</em> Paal-Knorr and Gewald cyclization strategies. A series of novel furan/thiophene selenocyanate derivatives were constructed by introducing selenocyanate groups with varying chain lengths through amide bonds. All compounds were structurally characterized using NMR and HR-MS analyses. MTT assay for antitumor activity revealed that several compounds exhibited superior efficacy compared to cisplatin. Notably, furan selenocyanate <strong>5c</strong> showed significant inhibitory activity against HepG-2 cells (IC<sub>50</sub> = 8.64 ± 0.94 μM), while thiophene selenocyanate <strong>11d</strong> demonstrated remarkable inhibition against HeLa and MCF-7 cells with IC<sub>50</sub> values of 6.39 and 6.77 μM, respectively. Structure-activity relationship (SAR) analysis indicated that the carbon chain length significantly influenced antitumor activity, with the C<sub>8</sub>-chain thiophene selenocyanate derivative <strong>11d</strong> exhibiting optimal selectivity for HeLa and MCF-7 cells. This study provides important references for development of novel selenium-containing antitumor drugs.</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"55 16","pages":"Pages 1257-1264"},"PeriodicalIF":1.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-18DOI: 10.1080/00397911.2025.2492703
Sherif M. H. Sanad (Conceptualization Investigation Methodology Project administration Resources Supervision Validation Writing – original draft Writing – review & editing) , Ibrahim S. Sanad (Conceptualization Data curation Formal analysis Investigation Methodology Project administration Resources Software Supervision Validation Visualization Writing – original draft Writing – review & editing)
Microwaves are a type of electromagnetic radiation that, when used in chemical reactions, offer a number of advantages, including energy efficiency, reduced reaction time, higher synthesis rate, reduced by-products, well-defined final products, high purity, and improved physicochemical properties. Therefore, microwaves have been widely used in both organic and inorganic synthesis. Cyclic 1,3-diketones are versatile precursors that could be used to prepare diverse molecular systems. Among them, indane-1,3-dione has been widely used to prepare diverse indeno-fused heterocycles and spiro-heterocyclic derivatives that demonstrated numerous biological applications. This review includes a survey of the available reports where indane-1,3-dione is annulated, resulting in heterocycles with bi-, tri-, tetra-, and pentacyclic rings under microwave irradiation. Moreover, the review investigates the utility of microwave-assisted reactions in the synthesis of indanone-based, spiro-molecular systems. The mechanistic postulates of some complex procedures are highlighted. Some comments are added to highlight the biological applications of the indeno-fused products.
{"title":"Indane-1,3-dione: Versatile precursor for the microwave-assisted synthesis of annulated and spiro-molecular systems","authors":"Sherif M. H. Sanad (Conceptualization Investigation Methodology Project administration Resources Supervision Validation Writing – original draft Writing – review & editing) , Ibrahim S. Sanad (Conceptualization Data curation Formal analysis Investigation Methodology Project administration Resources Software Supervision Validation Visualization Writing – original draft Writing – review & editing)","doi":"10.1080/00397911.2025.2492703","DOIUrl":"10.1080/00397911.2025.2492703","url":null,"abstract":"<div><div>Microwaves are a type of electromagnetic radiation that, when used in chemical reactions, offer a number of advantages, including energy efficiency, reduced reaction time, higher synthesis rate, reduced by-products, well-defined final products, high purity, and improved physicochemical properties. Therefore, microwaves have been widely used in both organic and inorganic synthesis. Cyclic 1,3-diketones are versatile precursors that could be used to prepare diverse molecular systems. Among them, indane-1,3-dione has been widely used to prepare diverse indeno-fused heterocycles and spiro-heterocyclic derivatives that demonstrated numerous biological applications. This review includes a survey of the available reports where indane-1,3-dione is annulated, resulting in heterocycles with bi-, tri-, tetra-, and pentacyclic rings under microwave irradiation. Moreover, the review investigates the utility of microwave-assisted reactions in the synthesis of indanone-based, spiro-molecular systems. The mechanistic postulates of some complex procedures are highlighted. Some comments are added to highlight the biological applications of the indeno-fused products.</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"55 14","pages":"Pages 1045-1071"},"PeriodicalIF":1.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Striatal Enriched protein tyrosine Phosphatase (STEP61) plays a crucial role in motor reflexes, cognition, and Alzheimer’s pathology. Despite its significance, STEP61’s exploration via in silico methods has been limited.
Method
We identified STEP61’s binding site using induced fit docking, screened a peptidomimetic library of 32,800 compounds for potential inhibitors, and synthesized top hits. Docking studies emphasized binding requirements within STEP61’s catalytic domain and WPD loop. Molecular dynamics simulations highlighted the importance of hydrophobic contacts and hydrogen bonding in complex stability.
Results
High Throughput Screening yielded promising docking scores (-11.4 to −3.8), with XP docking showing scores ranging from −6.6 to −7.6, indicating potential interaction and activity. Cα residues maintained RMSD values below 2 Å throughout simulations, ensuring structural stability. These findings lay the groundwork for developing novel STEP61 inhibitors, offering promising avenues for Alzheimer’s disease therapeutics.
{"title":"Design of peptidomimetic library: In-silico screening, molecular docking, synthesis and characterization of hits for STEP61","authors":"Pritam V. Bagwe (Conceptualization Data curation Methodology Software Writing – original draft Writing – review & editing) , Radni D. Deshpande (Data curation Visualization) , Gabor Juhasz (Supervision Visualization) , Sadhana Sathaye (Funding acquisition Investigation Visualization) , Shreerang V. Joshi (Project administration Resources Supervision Validation Visualization Writing – review & editing)","doi":"10.1080/00397911.2025.2526018","DOIUrl":"10.1080/00397911.2025.2526018","url":null,"abstract":"<div><h3>Introduction</h3><div>Striatal Enriched protein tyrosine Phosphatase (STEP61) plays a crucial role in motor reflexes, cognition, and Alzheimer’s pathology. Despite its significance, STEP61’s exploration via in silico methods has been limited.</div></div><div><h3>Method</h3><div>We identified STEP61’s binding site using induced fit docking, screened a peptidomimetic library of 32,800 compounds for potential inhibitors, and synthesized top hits. Docking studies emphasized binding requirements within STEP61’s catalytic domain and WPD loop. Molecular dynamics simulations highlighted the importance of hydrophobic contacts and hydrogen bonding in complex stability.</div></div><div><h3>Results</h3><div>High Throughput Screening yielded promising docking scores (-11.4 to −3.8), with XP docking showing scores ranging from −6.6 to −7.6, indicating potential interaction and activity. Cα residues maintained RMSD values below 2 Å throughout simulations, ensuring structural stability. These findings lay the groundwork for developing novel STEP61 inhibitors, offering promising avenues for Alzheimer’s disease therapeutics.</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"55 14","pages":"Pages 1072-1088"},"PeriodicalIF":1.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-18DOI: 10.1080/00397911.2025.2524706
Nariman R. Abd Elaal (Formal analysis Writing – original draft) , Sayed A. Ahmed (Formal analysis Writing – original draft) , Mamdouh A. Abu-Zaied (Conceptualization Data curation Formal analysis Investigation Methodology Resources Supervision Validation Visualization Writing – original draft Writing – review & editing)
A new series of pyrimidine thioglycosides incorporating pyrazole derivative, were synthesized via condensation of -pyrazole-4-carbaldehyde derivative 1 with substituted acetophenones 2a–d in basic medium, to afford new (E) chalcones 3a–d, the resulting compounds underwent cyclocondensation reactions with thiourea to yield sodium pyrimidine-2-thiolate derivatives 5a–d. The desired pyrimidine thioglycoside 8a–h were synthesized by the coupling of aglycone 5a-d with α-bromo per-acetylated sugars 7a,b in DMF at room temperature. On the other hand, the treatment of pyrimidine-2-thiolate salts 5a–d with HCl resulted in the formation of pyrimidine-2-thiole derivatives 6a–d. These derivatives, when stirred with α-D-gluco- and galacto-pyranosyl bromides in NaH and DMF solution produced the corresponding pyrimidine thioglycosides 8a–h. Some of the later compounds were subjected to NH3 in methanol at 0 °C to afford the unprotected thioglycoside functionalized compounds 9a–c with good yields. Seven of newly synthesized compounds were evaluated for their anticancer activities against 2-cell lines MCF-7 (breast) and HEPG2 (liver).
以-吡唑-4-乙醛衍生物1为原料，在碱性介质中与取代苯乙酮2- d缩合，得到新的(E)查尔酮3 - d，并与硫脲进行环缩合反应，得到嘧啶-2-硫酸钠衍生物5 - d。以α-溴过乙酰化糖7a、b与5 -a -d糖苷元在DMF中偶联，在室温下合成了所需的嘧啶巯基糖苷8a-h。另一方面，用盐酸处理嘧啶-2-硫代盐5a-d，生成嘧啶-2-硫代衍生物6a-d。这些衍生物与α- d -葡萄糖和半乳糖吡喃基溴化物在NaH和DMF溶液中搅拌后产生相应的嘧啶巯基苷8a-h。随后的一些化合物在0℃的甲醇中进行NH3反应，得到了产率较高的无保护的巯基糖苷功能化化合物9a-c。7个新合成的化合物对2种细胞系MCF-7（乳腺）和HEPG2（肝脏）的抗癌活性进行了评价。
{"title":"Synthesis of novel pyrazole-pyrimidine thioglycoside hybrids as anticancer agents","authors":"Nariman R. Abd Elaal (Formal analysis Writing – original draft) , Sayed A. Ahmed (Formal analysis Writing – original draft) , Mamdouh A. Abu-Zaied (Conceptualization Data curation Formal analysis Investigation Methodology Resources Supervision Validation Visualization Writing – original draft Writing – review & editing)","doi":"10.1080/00397911.2025.2524706","DOIUrl":"10.1080/00397911.2025.2524706","url":null,"abstract":"<div><div>A new series of pyrimidine thioglycosides incorporating pyrazole derivative, were synthesized via condensation of -pyrazole-4-carbaldehyde derivative <strong>1</strong> with substituted acetophenones <strong>2a–d</strong> in basic medium, to afford new (<em>E</em>) chalcones <strong>3a–d</strong>, the resulting compounds underwent cyclocondensation reactions with thiourea to yield sodium pyrimidine-2-thiolate derivatives <strong>5a–d</strong>. The desired pyrimidine thioglycoside <strong>8a–h</strong> were synthesized by the coupling of aglycone <strong>5a-d</strong> with α-bromo per-acetylated sugars <strong>7a,b</strong> in DMF at room temperature. On the other hand, the treatment of pyrimidine-2-thiolate salts <strong>5a–d</strong> with HCl resulted in the formation of pyrimidine-2-thiole derivatives <strong>6a–d</strong>. These derivatives, when stirred with α-D-gluco- and galacto-pyranosyl bromides in NaH and DMF solution produced the corresponding pyrimidine thioglycosides <strong>8a–h</strong>. Some of the later compounds were subjected to NH<sub>3</sub> in methanol at 0 °C to afford the unprotected thioglycoside functionalized compounds <strong>9a–c</strong> with good yields. Seven of newly synthesized compounds were evaluated for their anticancer activities against 2-cell lines MCF-7 (breast) and HEPG2 (liver).</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"55 14","pages":"Pages 1099-1112"},"PeriodicalIF":1.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-18DOI: 10.1080/00397911.2025.2526802
Monil P. Dholariya (Conceptualization Data curation Investigation Methodology Software Validation Visualization Writing – original draft) , Mital J. Kaneria (Formal analysis Investigation Software Validation) , Anilkumar S. Patel (Data curation Formal analysis Investigation Resources Supervision Validation Writing – review & editing)
In this study, we synthesized a series of biphenylcarbonitrile–triazole–thiazolidinedione hybrids and evaluated their α-amylase inhibitory activity. The synthesized compounds were obtained in excellent yields and fully characterized using 1H and 13C NMR, IR and mass spectrometry. Biological evaluation revealed potent α-amylase inhibition, with IC50 values ranging from 1.01 to 5.14 μM. Notably, compound 5p exhibited the strongest inhibitory activity (IC50 = 1.01 ± 0.02 μM), surpassing the standard drug Acarbose (IC50 = 1.32 ± 0.04 μM). Furthermore, the enzyme inhibition kinetics study indicated that 5p functions as a competitive inhibitor, with Ki value of 0.47 μM. Molecular docking studies confirmed the formation of stable protein-ligand complexes within the active site of α-amylase. Additionally, ADMET predictions indicated that 5p possesses favorable pharmacokinetic properties with minimal toxicity, including the absence of hepatotoxicity and skin sensitization risks. These findings suggest that compound 5p holds promise as a potential safe and effective anti-diabetic agent.
{"title":"Exploring biphenylcarbonitrile–triazole–thiazolidinedione hybrids as antidiabetic agents: Synthesis, α-amylase inhibition, Molecular docking, and ADMET insights","authors":"Monil P. Dholariya (Conceptualization Data curation Investigation Methodology Software Validation Visualization Writing – original draft) , Mital J. Kaneria (Formal analysis Investigation Software Validation) , Anilkumar S. Patel (Data curation Formal analysis Investigation Resources Supervision Validation Writing – review & editing)","doi":"10.1080/00397911.2025.2526802","DOIUrl":"10.1080/00397911.2025.2526802","url":null,"abstract":"<div><div>In this study, we synthesized a series of biphenylcarbonitrile–triazole–thiazolidinedione hybrids and evaluated their α-amylase inhibitory activity. The synthesized compounds were obtained in excellent yields and fully characterized using <sup>1</sup>H and <sup>13</sup>C NMR, IR and mass spectrometry. Biological evaluation revealed potent α-amylase inhibition, with IC<sub>50</sub> values ranging from 1.01 to 5.14 μM. Notably, compound <strong>5p</strong> exhibited the strongest inhibitory activity (IC<sub>50</sub> = 1.01 ± 0.02 μM), surpassing the standard drug Acarbose (IC<sub>50</sub> = 1.32 ± 0.04 μM). Furthermore, the enzyme inhibition kinetics study indicated that <strong>5p</strong> functions as a competitive inhibitor, with K<sub>i</sub> value of 0.47 μM. Molecular docking studies confirmed the formation of stable protein-ligand complexes within the active site of α-amylase. Additionally, ADMET predictions indicated that <strong>5p</strong> possesses favorable pharmacokinetic properties with minimal toxicity, including the absence of hepatotoxicity and skin sensitization risks. These findings suggest that compound <strong>5p</strong> holds promise as a potential safe and effective anti-diabetic agent.</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"55 14","pages":"Pages 1113-1129"},"PeriodicalIF":1.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-18DOI: 10.1080/00397911.2025.2526014
Sharad P. Panchgalle (Conceptualization Formal analysis Investigation Methodology Writing – original draft) , Yunnus B. Shaikh (Formal analysis Investigation Methodology) , Santosh D. Deosarkar (Data curation Validation Visualization) , Vijaykumar S. More (Conceptualization Methodology Project administration Resources Supervision Writing – review & editing)
An efficient asymmetric construction of chiral trisubstituted tetrahydrofuan core 1 achieved using D-mannitol as chiral starting material. The chiral glyceraldehyde, derived from D-mannitol, converted into alkene which on Clainsen rearrangement converted into chiral 2-substitutedpent-4-enal. The chiral aldehyde on reduction followed by protection subjected for allylic oxidation and afforded diastereomeric inseparable mixture of alcohols 3 and 3′. The mixture of 3 and 3′ was converted into separable mixture of benzyl ethers 2 and 2′. To confirm the stereochemistry of 2 and 2′, they were converted into acetonides 12 and 12′, respectively. Rychnovsky’s method was employed to confirm the absolute stereochemistry of 12 and 12′. Compound 2′ was converted into its diastereomer 2 by using Mitsunobu protocol. The compound 2 was converted into target compound 1 through NBS mediated cyclization. The stereochemistry of chiral trisubstituted tetrahydrofuran core 1 was resembling to THF core present in natural products Aureonitol and Musanahol.
{"title":"Stereoselective construction of 2,3,4-trisubstituted tetrahydrofuran core using NBS mediated cyclization","authors":"Sharad P. Panchgalle (Conceptualization Formal analysis Investigation Methodology Writing – original draft) , Yunnus B. Shaikh (Formal analysis Investigation Methodology) , Santosh D. Deosarkar (Data curation Validation Visualization) , Vijaykumar S. More (Conceptualization Methodology Project administration Resources Supervision Writing – review & editing)","doi":"10.1080/00397911.2025.2526014","DOIUrl":"10.1080/00397911.2025.2526014","url":null,"abstract":"<div><div>An efficient asymmetric construction of chiral trisubstituted tetrahydrofuan core <strong>1</strong> achieved using D-mannitol as chiral starting material. The chiral glyceraldehyde, derived from D-mannitol, converted into alkene which on Clainsen rearrangement converted into chiral 2-substitutedpent-4-enal. The chiral aldehyde on reduction followed by protection subjected for allylic oxidation and afforded diastereomeric inseparable mixture of alcohols <strong>3</strong> and <strong>3′</strong>. The mixture of <strong>3</strong> and <strong>3′</strong> was converted into separable mixture of benzyl ethers <strong>2</strong> and <strong>2′</strong>. To confirm the stereochemistry of <strong>2</strong> and <strong>2′</strong>, they were converted into acetonides <strong>12</strong> and <strong>12′</strong>, respectively. Rychnovsky’s method was employed to confirm the absolute stereochemistry of <strong>12</strong> and <strong>12′</strong>. Compound <strong>2′</strong> was converted into its diastereomer <strong>2</strong> by using Mitsunobu protocol. The compound <strong>2</strong> was converted into target compound <strong>1</strong> through NBS mediated cyclization. The stereochemistry of chiral trisubstituted tetrahydrofuran core <strong>1</strong> was resembling to THF core present in natural products Aureonitol and Musanahol.</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"55 14","pages":"Pages 1089-1098"},"PeriodicalIF":1.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-24DOI: 10.1080/00397911.2025.2520609
Aisha A. Alsfouk (Data curation Funding acquisition Methodology Validation Writing – original draft) , Benson M. Kariuki (Data curation Formal analysis Investigation Methodology Resources Software Validation Visualization Writing – original draft) , Asmaa Saleh (Data curation Funding acquisition Project administration Validation Visualization Writing – original draft) , Aladdin M. Srour (Conceptualization Investigation Methodology Supervision Validation Visualization Writing – original draft Writing – review & editing)
Three novel 4-piperidone-based derivatives (3a–c) were synthesized utilizing the base-catalyzed condensation method (KOH/EtOH) with aromatic aldehydes (2a–c) featuring secondary amine rings, specifically piperidine, morpholine, and methyl piperazine. The three newly synthesized derivatives were characterized through X-ray crystallography, and their anti-proliferative effects were assessed against three different human cancer cell lines: breast carcinoma (MCF-7), liver cancer (HepG-2), and colorectal carcinoma (HCT-116), along with a normal cell line (RPE1), following the MTT assay procedure. Among them, compound 3c demonstrated the highest efficacy against all tested cell lines, demonstrating IC50 = 1.07 ± 0.04 μM for MCF-7 and 2.55 ± 0.07 μM for HepG-2, compared to the standard reference, Doxorubicin, which had IC50 = 5.38 ± 0.05 μM and 4.25 ± 0.01 μM, respectively. Moreover, a molecular docking study confirmed the stable interaction of compound 3c within the ATP binding site of human cyclin-dependent kinase 2 (CDK2). This study introduces three promising intermediates for further research in medicinal chemistry.
{"title":"Synthesis, characterization, crystal structure and anti-proliferative properties of curcumin mimic conjugates","authors":"Aisha A. Alsfouk (Data curation Funding acquisition Methodology Validation Writing – original draft) , Benson M. Kariuki (Data curation Formal analysis Investigation Methodology Resources Software Validation Visualization Writing – original draft) , Asmaa Saleh (Data curation Funding acquisition Project administration Validation Visualization Writing – original draft) , Aladdin M. Srour (Conceptualization Investigation Methodology Supervision Validation Visualization Writing – original draft Writing – review & editing)","doi":"10.1080/00397911.2025.2520609","DOIUrl":"10.1080/00397911.2025.2520609","url":null,"abstract":"<div><div>Three novel 4-piperidone-based derivatives (<strong>3a–c</strong>) were synthesized utilizing the base-catalyzed condensation method (KOH/EtOH) with aromatic aldehydes (<strong>2a–c</strong>) featuring secondary amine rings, specifically piperidine, morpholine, and methyl piperazine. The three newly synthesized derivatives were characterized through X-ray crystallography, and their anti-proliferative effects were assessed against three different human cancer cell lines: breast carcinoma (MCF-7), liver cancer (HepG-2), and colorectal carcinoma (HCT-116), along with a normal cell line (RPE1), following the MTT assay procedure. Among them, compound <strong>3c</strong> demonstrated the highest efficacy against all tested cell lines, demonstrating IC<sub>50</sub> = 1.07 ± 0.04 μM for MCF-7 and 2.55 ± 0.07 μM for HepG-2, compared to the standard reference, Doxorubicin, which had IC<sub>50</sub> = 5.38 ± 0.05 μM and 4.25 ± 0.01 μM, respectively. Moreover, a molecular docking study confirmed the stable interaction of compound <strong>3c</strong> within the ATP binding site of human cyclin-dependent kinase 2 (CDK2). This study introduces three promising intermediates for further research in medicinal chemistry.</div></div>","PeriodicalId":22119,"journal":{"name":"Synthetic Communications","volume":"55 13","pages":"Pages 1029-1043"},"PeriodicalIF":1.8,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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