Elena Tretyakova, Liwen Hua, Anna Smirnova, Oxana Kazakova, Vladimir Zarubaev, Hongwei Jin, Huan Xu, Sulong Xiao
Abietane type diterpenic (dehydroabietic, 2,3‐dihydroquinopimaric and maleopimaric) acids were converted by the acid chloride method into a series of aliphatic and heterocyclic amine spacered conjugates. A number of structurally novel derivatives holding 1,2,3‐triazole moieties were designed and synthesized by treating of the propargylated amides and esters with a sugar azides using the Cu(I)‐catalyzed click chemistry approach. The synthesized N‐containing diterpene derivatives were tested for their potential inhibition of influenza A/PuertoRico/8/34 (H1N1) virus in MDCK cell culture and SARS‐CoV‐2 pseudovirus in BHK‐21‐hACE2 cells. Among tested forty‐five compounds ten derivatives were the most efficacious against influenza virus A with IC50 0.7‐63.4 μM together with high selectivity index SI value from 11 from 94. Dihydroquinopimaric acid N‐ethylpiperazine‐amide and dehydroabietic acid 1,2,3‐triazoles spacered with glucose and lactose showed anti‐SARS‐CoV‐2 pseudovirus activity with EC50 values of 1.79‐25.46 µM. Molecular docking and dynamics modeling investigated the binding mode of the lead compounds into the binding pocket of influenza A virus M2 protein and the RBD domain of SARS‐CoV‐2 spike glycoprotein.
{"title":"Novel Abietane type Sugar Triazole Hybrids and Amides against SARS‐CoV‐2 Spike Glycoprotein and Influenza A Virus","authors":"Elena Tretyakova, Liwen Hua, Anna Smirnova, Oxana Kazakova, Vladimir Zarubaev, Hongwei Jin, Huan Xu, Sulong Xiao","doi":"10.1002/ajoc.202400227","DOIUrl":"https://doi.org/10.1002/ajoc.202400227","url":null,"abstract":"Abietane type diterpenic (dehydroabietic, 2,3‐dihydroquinopimaric and maleopimaric) acids were converted by the acid chloride method into a series of aliphatic and heterocyclic amine spacered conjugates. A number of structurally novel derivatives holding 1,2,3‐triazole moieties were designed and synthesized by treating of the propargylated amides and esters with a sugar azides using the Cu(I)‐catalyzed click chemistry approach. The synthesized N‐containing diterpene derivatives were tested for their potential inhibition of influenza A/PuertoRico/8/34 (H1N1) virus in MDCK cell culture and SARS‐CoV‐2 pseudovirus in BHK‐21‐hACE2 cells. Among tested forty‐five compounds ten derivatives were the most efficacious against influenza virus A with IC50 0.7‐63.4 μM together with high selectivity index SI value from 11 from 94. Dihydroquinopimaric acid N‐ethylpiperazine‐amide and dehydroabietic acid 1,2,3‐triazoles spacered with glucose and lactose showed anti‐SARS‐CoV‐2 pseudovirus activity with EC50 values of 1.79‐25.46 µM. Molecular docking and dynamics modeling investigated the binding mode of the lead compounds into the binding pocket of influenza A virus M2 protein and the RBD domain of SARS‐CoV‐2 spike glycoprotein.","PeriodicalId":130,"journal":{"name":"Asian Journal of Organic Chemistry","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142227007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The combination of HBr, TMSO (tetramethylene sulfoxide) and HFIP (hexafluoroisopropanol) has been utilized in the modification of pyrrolo[2,1‐a]isoquinoline derivatives through bromination, dimerization and sulfenylation respectively. In these processes, HBr serves as the source of bromine and TMSO acts as an oxidant. HFIP also plays an essential role for the oxidative dimerization. Chemoselectivity can be easily controlled by adjusting the parameters such as reaction time, ratio of reagents and the addition of nucleophile.
{"title":"HBr/TMSO/HFIP Mediated Chemoselective Modifications of Pyrrolo[2,1‐a]isoquinolines","authors":"Hai-Lei Cui, Yun-Meng Li, Man Jiang, Jing Zhou","doi":"10.1002/ajoc.202400323","DOIUrl":"https://doi.org/10.1002/ajoc.202400323","url":null,"abstract":"The combination of HBr, TMSO (tetramethylene sulfoxide) and HFIP (hexafluoroisopropanol) has been utilized in the modification of pyrrolo[2,1‐a]isoquinoline derivatives through bromination, dimerization and sulfenylation respectively. In these processes, HBr serves as the source of bromine and TMSO acts as an oxidant. HFIP also plays an essential role for the oxidative dimerization. Chemoselectivity can be easily controlled by adjusting the parameters such as reaction time, ratio of reagents and the addition of nucleophile.","PeriodicalId":130,"journal":{"name":"Asian Journal of Organic Chemistry","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Photocatalytic sulfonylation/trifluoromethylation‐peroxidation of alkenes with N‐sulfonyl ketimines and tert‐butyl hydroperoxide is reported. The transformation is initiated by the EnT‐driven homolytic S‐N bond cleavage of N‐sulfonyl ketimines. The sulfonyl‐peroxides were obtained when alkyl sulfonyl radicals were captured by alkene via sequential C‐S and C‐O bond formation, while a thermodynamically favored release of SO2 from trifluoromethane sulfonyl radical generated CF3 radical and afforded the trifluoromethyl‐peroxides.
{"title":"Photo‐Induced Sulfonylation/Trifluoromethylation‐Peroxidation of Alkenes via EnT‐Mediated N–S Bond Homolysis of N‐Sulfonyl Ketimines","authors":"Yuting Feng, Leiyang Lv, Zhiping Li","doi":"10.1002/ajoc.202400384","DOIUrl":"https://doi.org/10.1002/ajoc.202400384","url":null,"abstract":"Photocatalytic sulfonylation/trifluoromethylation‐peroxidation of alkenes with N‐sulfonyl ketimines and tert‐butyl hydroperoxide is reported. The transformation is initiated by the EnT‐driven homolytic S‐N bond cleavage of N‐sulfonyl ketimines. The sulfonyl‐peroxides were obtained when alkyl sulfonyl radicals were captured by alkene via sequential C‐S and C‐O bond formation, while a thermodynamically favored release of SO2 from trifluoromethane sulfonyl radical generated CF3 radical and afforded the trifluoromethyl‐peroxides.","PeriodicalId":130,"journal":{"name":"Asian Journal of Organic Chemistry","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Considering the drawbacks associated with available synthetic methodologies of isoflavones, herein we have reported a metal-free and eco-friendly approach to these natural products. In the present study, we have carried out the synthesis of eight isoflavone derivatives 7a-7h using α-aryl-β,β-ditosyloxy ketones protocol. Initially, we have protected the 2’-hydroxy group of respective chalcone moiety in order to remove its interference under reaction conditions. The 2’-protected chalcones were then subjected to 1,2-aryl migration by being treated with hydroxy(tosyloxy)iodobenzene (HTIB) reagent in a non-nucleophilic solvent (CH2Cl2). This migration furnished the formation of α-aryl-β,β-ditosyloxy ketones via C-C bond formation from their corresponding chalcones in moderate to good yields (55-82%). The ambiguity regarding the exact molecular structure of the α-aryl-β,β-ditosyloxy ketones was examined through the single crystal X-ray diffraction data. At last, the synthesis of isoflavones was carried in moderate to good yields (50-80%) out by performing the reaction of α-aryl-β,β-ditosyloxy ketones with sodium hydroxide in aqueous methanol.
{"title":"FACILE AND METAL-FREE SYNTHESIS OF ISOFLAVONES USING α-ARYL-β,β-DITOSYLOXY KETONES","authors":"Omkar Bains, Ashish Kumar, Raj Kamal, Ravinder Kumar, Rajesh Kumar, Tanmay Rom, Avijit Kumar Paul","doi":"10.1002/ajoc.202400336","DOIUrl":"https://doi.org/10.1002/ajoc.202400336","url":null,"abstract":"Considering the drawbacks associated with available synthetic methodologies of isoflavones, herein we have reported a metal-free and eco-friendly approach to these natural products. In the present study, we have carried out the synthesis of eight isoflavone derivatives 7a-7h using α-aryl-β,β-ditosyloxy ketones protocol. Initially, we have protected the 2’-hydroxy group of respective chalcone moiety in order to remove its interference under reaction conditions. The 2’-protected chalcones were then subjected to 1,2-aryl migration by being treated with hydroxy(tosyloxy)iodobenzene (HTIB) reagent in a non-nucleophilic solvent (CH2Cl2). This migration furnished the formation of α-aryl-β,β-ditosyloxy ketones via C-C bond formation from their corresponding chalcones in moderate to good yields (55-82%). The ambiguity regarding the exact molecular structure of the α-aryl-β,β-ditosyloxy ketones was examined through the single crystal X-ray diffraction data. At last, the synthesis of isoflavones was carried in moderate to good yields (50-80%) out by performing the reaction of α-aryl-β,β-ditosyloxy ketones with sodium hydroxide in aqueous methanol.","PeriodicalId":130,"journal":{"name":"Asian Journal of Organic Chemistry","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sari Deketelaere, Carlos Diez-Poza, Margot Aelbrecht, Jonas Mortier, Bram Van Den Bossche, Jorick Franceus, Tom Desmet, Kristof Van Hecke, Chris Stevens, Matthias D'hooghe
A synthetic protocol for the preparation of novel 3,4-pyrrolidine-fused β-lactams was developed. The proposed 2,6-diazabicyclo[3.2.0]heptan-7-one scaffolds were constructed through an amido group-induced, potassium tert-butoxide-promoted intramolecular ring closure of 3-acylamino-4-oxiranyl-β-lactams as the key reaction step. Alternatively, the desired cyclization was also effected by means of a scandium triflate-mediated catalytic approach. In this way, a set of stereodefined 3,4-pyrrolidine-fused β-lactams was synthesized, which were preliminary evaluated as β-lactamase inhibitors. These first-line biological assessments led to the identification of a 2-benzoyl-6-(4-methoxyphenyl)-substituted diazabicyclo structure as an eligible starting point for further β-lactamase inhibitor optimization studies.
{"title":"Synthesis of pyrrolidine-fused β-lactams as potential β-lactamase inhibitors","authors":"Sari Deketelaere, Carlos Diez-Poza, Margot Aelbrecht, Jonas Mortier, Bram Van Den Bossche, Jorick Franceus, Tom Desmet, Kristof Van Hecke, Chris Stevens, Matthias D'hooghe","doi":"10.1002/ajoc.202400364","DOIUrl":"https://doi.org/10.1002/ajoc.202400364","url":null,"abstract":"A synthetic protocol for the preparation of novel 3,4-pyrrolidine-fused β-lactams was developed. The proposed 2,6-diazabicyclo[3.2.0]heptan-7-one scaffolds were constructed through an amido group-induced, potassium tert-butoxide-promoted intramolecular ring closure of 3-acylamino-4-oxiranyl-β-lactams as the key reaction step. Alternatively, the desired cyclization was also effected by means of a scandium triflate-mediated catalytic approach. In this way, a set of stereodefined 3,4-pyrrolidine-fused β-lactams was synthesized, which were preliminary evaluated as β-lactamase inhibitors. These first-line biological assessments led to the identification of a 2-benzoyl-6-(4-methoxyphenyl)-substituted diazabicyclo structure as an eligible starting point for further β-lactamase inhibitor optimization studies.","PeriodicalId":130,"journal":{"name":"Asian Journal of Organic Chemistry","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qian-Qian Wu, Yan Wang, Muliang Zhang, Shi-Kai Tian
The poor nucleofugality of the amino group renders the C–N bond functionalization of primary aromatic amines highly challenging. Herein, we report a direct substitution reaction of 2‐aminotropones, bearing a unique non‐benzenoid seven‐membered aromatic ring that exists in some natural products and bioactive molecules, with potassium allyltrifluoroborates through C–N bond cleavage under transition‐metal‐free conditions. The amino group of 2‐aminotropones were directly substituted with potassium allyltrifluoroborates in the presence of sodium bicarbonate, delivering structurally diverse 2‐allyltropones in moderate to good yields. The reaction is free of directing groups, activating groups and transition metals, providing a convenient method to access substituted tropones.
{"title":"Direct Substitution of 2‐Aminotropones with Potassium Allyltrifluoroborates through Transition‐Metal‐Free C–N Bond Cleavage","authors":"Qian-Qian Wu, Yan Wang, Muliang Zhang, Shi-Kai Tian","doi":"10.1002/ajoc.202400386","DOIUrl":"https://doi.org/10.1002/ajoc.202400386","url":null,"abstract":"The poor nucleofugality of the amino group renders the C–N bond functionalization of primary aromatic amines highly challenging. Herein, we report a direct substitution reaction of 2‐aminotropones, bearing a unique non‐benzenoid seven‐membered aromatic ring that exists in some natural products and bioactive molecules, with potassium allyltrifluoroborates through C–N bond cleavage under transition‐metal‐free conditions. The amino group of 2‐aminotropones were directly substituted with potassium allyltrifluoroborates in the presence of sodium bicarbonate, delivering structurally diverse 2‐allyltropones in moderate to good yields. The reaction is free of directing groups, activating groups and transition metals, providing a convenient method to access substituted tropones.","PeriodicalId":130,"journal":{"name":"Asian Journal of Organic Chemistry","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yizhou Li, Tianyang Zhang, Xianfu Fang, Xin Wang, Huicong Wang, Gong Zhang, Wei Fang, Yangfeng Li
Primary amides play a crucial role in organic and pharmaceutical synthesis. Herein, we present a rapid and convenient method for transforming diverse DNA‐conjugated nitriles into primary amides utilizing hydrogen peroxide and potassium carbonate. The substrate scope and DEL compatibility of this reaction were thoroughly investigated, revealing a wide range of substrates with moderate‐to‐excellent conversion. This on‐DNA transformation holds significant promise for constructing DNA‐encoded libraries (DELs) and enabling late‐stage functionalization to expand chemical diversity. Our approach not only highlights the versatility of the method but also underscores its potential for broad applications in organic and pharmaceutical synthesis.
伯胺在有机合成和药物合成中起着至关重要的作用。在此，我们提出了一种利用过氧化氢和碳酸钾将各种 DNA 键合腈类转化为伯胺的快速便捷方法。我们对这一反应的底物范围和 DEL 兼容性进行了深入研究，发现了多种具有中等至优异转化率的底物。这种 DNA 上的转化为构建 DNA 编码文库（DELs）和实现后期功能化以扩大化学多样性带来了重大希望。我们的方法不仅凸显了该方法的多功能性，还强调了它在有机合成和药物合成中的广泛应用潜力。
{"title":"DNA‐Compatible Nitriles Hydrolysis for Late‐Stage Functionalization of DNA‐Encoded Libraries","authors":"Yizhou Li, Tianyang Zhang, Xianfu Fang, Xin Wang, Huicong Wang, Gong Zhang, Wei Fang, Yangfeng Li","doi":"10.1002/ajoc.202400280","DOIUrl":"https://doi.org/10.1002/ajoc.202400280","url":null,"abstract":"Primary amides play a crucial role in organic and pharmaceutical synthesis. Herein, we present a rapid and convenient method for transforming diverse DNA‐conjugated nitriles into primary amides utilizing hydrogen peroxide and potassium carbonate. The substrate scope and DEL compatibility of this reaction were thoroughly investigated, revealing a wide range of substrates with moderate‐to‐excellent conversion. This on‐DNA transformation holds significant promise for constructing DNA‐encoded libraries (DELs) and enabling late‐stage functionalization to expand chemical diversity. Our approach not only highlights the versatility of the method but also underscores its potential for broad applications in organic and pharmaceutical synthesis.","PeriodicalId":130,"journal":{"name":"Asian Journal of Organic Chemistry","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We investigated how the introduction of substituent at the 9‐ or 10‐position of the 1,8‐dichloroanthracene framework affects the horizontal and vertical distortions of the anthracene rings. The 9‐substituted anthracenes showed higher distortions than their 10‐substituted counterparts due to the steric repulsion with two chloro groups at the peri‐positions. The distortion of anthracene framework affected their reactivity. Indeed, 9‐substituted anthracenes exhibited higher reactivity to undergo the Diels–Alder reaction with maleic anhydride, which was a result of non‐electronic activation.
{"title":"Non‐Electronic Activation of Anthracenes Using Steric Repulsion of the 9‐Substituent with Chloro Groups at the peri‐Positions","authors":"Annisa Indah Reza, Kento Iwai, Nagatoshi Nishiwaki","doi":"10.1002/ajoc.202400381","DOIUrl":"https://doi.org/10.1002/ajoc.202400381","url":null,"abstract":"We investigated how the introduction of substituent at the 9‐ or 10‐position of the 1,8‐dichloroanthracene framework affects the horizontal and vertical distortions of the anthracene rings. The 9‐substituted anthracenes showed higher distortions than their 10‐substituted counterparts due to the steric repulsion with two chloro groups at the peri‐positions. The distortion of anthracene framework affected their reactivity. Indeed, 9‐substituted anthracenes exhibited higher reactivity to undergo the Diels–Alder reaction with maleic anhydride, which was a result of non‐electronic activation.","PeriodicalId":130,"journal":{"name":"Asian Journal of Organic Chemistry","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiahao Liu, Jiachun Nie, Zhe Wang, Terumasa Kato, Yan Liu, Keiji Maruoka
Cu‐ and Fe‐ catalyzed trideuteromethylation reactions using alkylsilyl peroxide as trideuteromethyl radical precursor are reported. The alkylsilyl peroxide was synthesized from acetone‐d6 in a three‐step sequence, and the reactions with various coupling partners afforded efficiently the corresponding N–CD3, O–CD3 and C–CD3 bond formation products. The radical heptadeuteriopropylation using alkylsilyl peroxide prepared from butyric acid‐d7 is also described.
{"title":"Facile Generation of Trideuteromethyl Radical from Alkylsilyl Peroxide and Subsequent Functionalization","authors":"Jiahao Liu, Jiachun Nie, Zhe Wang, Terumasa Kato, Yan Liu, Keiji Maruoka","doi":"10.1002/ajoc.202400382","DOIUrl":"https://doi.org/10.1002/ajoc.202400382","url":null,"abstract":"Cu‐ and Fe‐ catalyzed trideuteromethylation reactions using alkylsilyl peroxide as trideuteromethyl radical precursor are reported. The alkylsilyl peroxide was synthesized from acetone‐d6 in a three‐step sequence, and the reactions with various coupling partners afforded efficiently the corresponding N–CD3, O–CD3 and C–CD3 bond formation products. The radical heptadeuteriopropylation using alkylsilyl peroxide prepared from butyric acid‐d7 is also described.","PeriodicalId":130,"journal":{"name":"Asian Journal of Organic Chemistry","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The present article demonstrates the regioselective synthesis, characterization, and biological evaluation of eighteen novel pyrazolo‐benzothiazole hybrid molecules 5a‐5r. We have utilized β,β‐ditosyloxy ketones protocol to synthesize these hybrid molecules. The synthesized compounds were tested for their in‐vitro antiproliferative activities using MTT assay against breast cancer (MCF‐7), cervical cancer (HeLa), and Lung cancer (A549) cell lines. Hybrid molecules 5a, 5m, 5n, and 5o with IC50 values of 0.359 mM, 0.051 mM, 0.079 mM, and 0.259 mM respectively exhibited admirable growth inhibitory activities against MCF‐7 cancer cells even better than reference carboplatin drug having IC50 (0.439 mM). Compound 5k with IC50 value of 0.765 mM was found to be the most potent antiproliferative agent for the HeLa cancer cells. Moreover, hybrid molecule 5f with IC50 value of 0.706 mM exhibited better inhibitory activity against A549 cancer cells in comparison to the reference carboplatin drug having IC50 (0.805 mM). The mechanism of cellular toxicity was studied using Annexin V‐FITC/PI double staining method and cell cycle assay. Molecular docking studies for all the synthesized compounds have been performed in the binding pocket of VEGFR‐2 sites (PBD code: 4ASD). Finally, the ADMET profile of the potent molecules was also investigated to predict their drug‐likeness behaviour.
{"title":"Synthesis, anticancer evaluation, in‐silico ADMET and molecular docking studies for tailored pyrazolo‐benzothiazole hybrids","authors":"Omkar Bains, Ashish Kumar, Raj Kamal, Rasdeep Kour, Simrandeep Kaur, Satwinderjeet Kaur, Raman Jangra, Purshotam Sharma, Ravinder Kumar","doi":"10.1002/ajoc.202400187","DOIUrl":"https://doi.org/10.1002/ajoc.202400187","url":null,"abstract":"The present article demonstrates the regioselective synthesis, characterization, and biological evaluation of eighteen novel pyrazolo‐benzothiazole hybrid molecules 5a‐5r. We have utilized β,β‐ditosyloxy ketones protocol to synthesize these hybrid molecules. The synthesized compounds were tested for their in‐vitro antiproliferative activities using MTT assay against breast cancer (MCF‐7), cervical cancer (HeLa), and Lung cancer (A549) cell lines. Hybrid molecules 5a, 5m, 5n, and 5o with IC50 values of 0.359 mM, 0.051 mM, 0.079 mM, and 0.259 mM respectively exhibited admirable growth inhibitory activities against MCF‐7 cancer cells even better than reference carboplatin drug having IC50 (0.439 mM). Compound 5k with IC50 value of 0.765 mM was found to be the most potent antiproliferative agent for the HeLa cancer cells. Moreover, hybrid molecule 5f with IC50 value of 0.706 mM exhibited better inhibitory activity against A549 cancer cells in comparison to the reference carboplatin drug having IC50 (0.805 mM). The mechanism of cellular toxicity was studied using Annexin V‐FITC/PI double staining method and cell cycle assay. Molecular docking studies for all the synthesized compounds have been performed in the binding pocket of VEGFR‐2 sites (PBD code: 4ASD). Finally, the ADMET profile of the potent molecules was also investigated to predict their drug‐likeness behaviour.","PeriodicalId":130,"journal":{"name":"Asian Journal of Organic Chemistry","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142217023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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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