Pub Date : 2024-10-09DOI: 10.1134/S1068162024050157
M. Nazir, U. Khan, M. Jahangir
Objective: The study commenced with the conversion of 4-(1H-indol-3-yl)butanoic acid (I) into ethyl 4-(1H-indol-3-yl)butanoate (II), succeeded by the synthesis of the hydrazide nucleophile, 4-(1H-indol-3-yl)butanohydrazide (III). Methods: Following this, nucleophilic addition reactions of (III) with various electrophilic aldehydes (IVa–IVg) were conducted to yield the targeted derivatives (Va–Vg/Vʹa–Vʹg). The structural elucidation of all synthesized compounds relied on IR, 1H, 13C NMR, HMBC, and CHN analysis. Results and Discussion: Evaluation of the inhibitory effects of these heterocyclic butanohydrazides (Va–Vg/Vʹa–Vʹg) against the α-glucosidase enzyme revealed significant inhibition by compounds (Vg/Vʹg) compared to the standard. Conclusions: Hemolytic analysis indicated mild cytotoxicity towards red blood cell membranes, indicating the potential of these molecules as nontoxic medicinal scaffolds for skin pigmentation and related disorders.
{"title":"Synthesis, In Vitro and In Silico Investigations of 4-(1H-Indol-3-yl)-N′-[(E/Z)-(phenyl-substituted)methylidene] as Effective Inhibitors of α-Glucosidase","authors":"M. Nazir, U. Khan, M. Jahangir","doi":"10.1134/S1068162024050157","DOIUrl":"10.1134/S1068162024050157","url":null,"abstract":"<p><b>Objective:</b> The study commenced with the conversion of 4-(1<i>H</i>-indol-3-yl)butanoic acid (<b>I</b>) into ethyl 4-(1<i>H</i>-indol-3-yl)butanoate (<b>II</b>), succeeded by the synthesis of the hydrazide nucleophile, 4-(1<i>H</i>-indol-3-yl)butanohydrazide (<b>III</b>). <b>Methods:</b> Following this, nucleophilic addition reactions of (<b>III</b>) with various electrophilic aldehydes (<b>IVa–IVg</b>) were conducted to yield the targeted derivatives (<b>Va–Vg</b>/<b>Vʹa–Vʹg</b>). The structural elucidation of all synthesized compounds relied on IR, <sup>1</sup>H, <sup>13</sup>C NMR, HMBC, and CHN analysis. <b>Results and Discussion:</b> Evaluation of the inhibitory effects of these heterocyclic butanohydrazides (<b>Va–Vg</b>/<b>Vʹa–Vʹg</b>) against the α-glucosidase enzyme revealed significant inhibition by compounds (<b>Vg/Vʹg</b>) compared to the standard. <b>Conclusions:</b> Hemolytic analysis indicated mild cytotoxicity towards red blood cell membranes, indicating the potential of these molecules as nontoxic medicinal scaffolds for skin pigmentation and related disorders.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 5","pages":"1998 - 2012"},"PeriodicalIF":1.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142410995","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}
Pub Date : 2024-10-09DOI: 10.1134/S1068162024050121
K. J. Pansuriya, I. J. Modasiya, G. G. Dubal
Objective: In the present work synthesis and characterization of new heterocyclic derivatives containing dihydropyrano[2,3-c]pyrazoles. Methods: Synthesis of compounds was done using the conventional method via multicomponent reaction using substituted aldehyde, hydrazine hydrate or phenyl hydrazine, malononitrile, and L-proline as a catalyst with good yield. Reaction optimization is also performed. Results and Discussion: All synthesized compounds were tested for their in vitro anti-inflammatory and a comparison was done against the standard drug Diclofenac sodium. Conclusions: Some of the newly synthesized compounds demonstrated good to moderate anti-inflammatory activity.
{"title":"L-Proline Catalyzed Synthesis of Dihydropyrano[2,3-c]pyrazoles and Their Anti-Inflammatory Activity","authors":"K. J. Pansuriya, I. J. Modasiya, G. G. Dubal","doi":"10.1134/S1068162024050121","DOIUrl":"10.1134/S1068162024050121","url":null,"abstract":"<p><b>Objective:</b> In the present work synthesis and characterization of new heterocyclic derivatives containing dihydropyrano[2,3-<i>c</i>]pyrazoles. <b>Methods:</b> Synthesis of compounds was done using the conventional method <i>via</i> multicomponent reaction using substituted aldehyde, hydrazine hydrate or phenyl hydrazine, malononitrile, and L-proline as a catalyst with good yield. Reaction optimization is also performed. <b>Results and Discussion:</b> All synthesized compounds were tested for their <i>in vitro</i> anti-inflammatory and a comparison was done against the standard drug Diclofenac sodium. <b>Conclusions:</b> Some of the newly synthesized compounds demonstrated good to moderate anti-inflammatory activity.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 5","pages":"1935 - 1942"},"PeriodicalIF":1.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142410887","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}
Pub Date : 2024-10-09DOI: 10.1134/S1068162024050212
Arti Soni, Ashwani Kumar, Vivek Kumar
Objective: synthesize thioacetamide-thiazole as key pharmacophore possessing acetylcholinesterase (AChE) inhibitory activity. Methods: Thirteen compounds (IIIa–IIIm) were synthesized by preparing differently substituted aminothiazoles and subsequently evaluated for AChE inhibitory and antioxidant activity. Results and Discussion: Compound (IIIk) (IC50 = 1.99 µM) exhibits promising AChE inhibitory activity amongvarious derivatives of the series. The antioxidant potential of synthesized compounds were determined by DPPH assay (IC50 = 1.10 to 15.45 µM). Compound (IIIk) exhibited the utmost antioxidant activity with IC50 = 1.10 µM. Further molecular docking, drug-likeness, and ADMET predictions of all synthesized compounds were also assessed with computational methods. The results unequivocally supported the in vitro studies of all derivatives by displaying good docking score with binding pocket of PDB4EY7. Conclusions: The study concluded that compound (IIIk) emerged as potential lead compound as AChE inhibitor for the development of new compounds as anti-Alzheimer’s candidates.
{"title":"Synthesis of Thioacetamide-Thiazoles as Anticholinesterase and Antioxidant Agents against Alzheimer’s Disease","authors":"Arti Soni, Ashwani Kumar, Vivek Kumar","doi":"10.1134/S1068162024050212","DOIUrl":"10.1134/S1068162024050212","url":null,"abstract":"<p><b>Objective:</b> synthesize thioacetamide-thiazole as key pharmacophore possessing acetylcholinesterase (AChE) inhibitory activity. <b>Methods:</b> Thirteen compounds (<b>IIIa–IIIm</b>) were synthesized by preparing differently substituted aminothiazoles and subsequently evaluated for AChE inhibitory and antioxidant activity. <b>Results and Discussion:</b> Compound (<b>IIIk</b>) (IC<sub>50</sub> = 1.99 µM) exhibits promising AChE inhibitory activity amongvarious derivatives of the series. The antioxidant potential of synthesized compounds were determined by DPPH assay (IC<sub>50</sub> = 1.10 to 15.45 µM). Compound (<b>IIIk</b>) exhibited the utmost antioxidant activity with IC<sub>50</sub> = 1.10 µM. Further molecular docking, drug-likeness, and ADMET predictions of all synthesized compounds were also assessed with computational methods. The results unequivocally supported the <i>in vitro</i> studies of all derivatives by displaying good docking score with binding pocket of PDB4EY7. <b>Conclusions:</b> The study concluded that compound (<b>IIIk</b>) emerged as potential lead compound as AChE inhibitor for the development of new compounds as anti-Alzheimer’s candidates.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 5","pages":"1646 - 1658"},"PeriodicalIF":1.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142410911","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}
Pub Date : 2024-10-09DOI: 10.1134/S1068162024050376
О. А. Nurkenov, S. D. Fazylov, E. М. Satbayeva, Т. М. Seilkhanov, А. Zh. Mendibayeva, S. K. Kabiyeva, Sh. N. Tursymbek
Objective: The aim of this study is to produce novel of the new functionally substituted nicotinohydrazones, analyze their anti-inflammatory activity, and assess their toxicity. A promising avenue for the advancement of novel bioactive compounds is the pursuit of “hybrid molecules” that contain pharmacophore fragments within their structural composition, with a particular focus on the examination of these molecules for the discovery of novel biological activities. Methods: The synthesis of nicotinic acid hydrazones (II–VI) was performed by condensation of nicotinic acid hydrazide with various aldehydes in ethanol when refluxing the reaction mixture at 60–70°C. The anti-inflammatory activity was studied using the formalin paw edema method in non-linear white rats. The acute inflammatory reaction was reproduced by subplantar (i.e., underplantar or plantar aponeurosis) injection of 0.1 mL of a 2% formalin solution into the right paw using a conventional insulin syringe. Results and Discussion: The structure of the new functionally substituted nicotinohydrazones has been confirmed by a combination of the 1H and 13C NMR methods, and COSY (1H-1H), HMQC (1H–13C), and HMBC (1H–13C) two-dimensional NMR spectroscopy methods.1H, and 13C NMR spectroscopy were used to investigate all the prepared derivatives. The acute toxicity of the aforementioned compounds was preliminarily evaluated using a specially developed Toxicity Assessment Software Tool within the United States Environmental Protection Agency. The LD50 values for rats following oral administration of the compounds tested by the QSAR method. According to the projected toxicological effects, compounds (II), (III) can be classified into Class 4 in terms of toxicity. Compounds (IV), (V) and (VI) have low toxicity and very low toxicity, respectively. Conclusions: The anti-inflammatory activity of the synthesized hydrazones has been evaluated and it has been demonstrated that these compounds were ineffective in comparison with ibuprofen at a dosage of 100 mg/kg (p2 < 0.05). The low toxicity level of all the tested compounds was predicted by the computer modeling. The LD50 values of the compounds range from 445.461 to 1491.991 mg/kg. The studies on the model of formalin paw edema in nonlinear white rats indicate the absence of an anti-inflammatory effect of the tested compounds.
{"title":"Synthesis and Study Anti-Inflammatory Activity of Nicotinic Acid Hydrazones","authors":"О. А. Nurkenov, S. D. Fazylov, E. М. Satbayeva, Т. М. Seilkhanov, А. Zh. Mendibayeva, S. K. Kabiyeva, Sh. N. Tursymbek","doi":"10.1134/S1068162024050376","DOIUrl":"10.1134/S1068162024050376","url":null,"abstract":"<p><b>Objective:</b> The aim of this study is to produce novel of the new functionally substituted nicotinohydrazones, analyze their anti-inflammatory activity, and assess their toxicity. A promising avenue for the advancement of novel bioactive compounds is the pursuit of “hybrid molecules” that contain pharmacophore fragments within their structural composition, with a particular focus on the examination of these molecules for the discovery of novel biological activities. <b>Methods:</b> The synthesis of nicotinic acid hydrazones (<b>II–VI</b>) was performed by condensation of nicotinic acid hydrazide with various aldehydes in ethanol when refluxing the reaction mixture at 60–70°C. The anti-inflammatory activity was studied using the formalin paw edema method in non-linear white rats. The acute inflammatory reaction was reproduced by subplantar (i.e., underplantar or plantar aponeurosis) injection of 0.1 mL of a 2% formalin solution into the right paw using a conventional insulin syringe. <b>Results and Discussion:</b> The structure of the new functionally substituted nicotinohydrazones has been confirmed by a combination of the <sup>1</sup>H and <sup>13</sup>C NMR methods, and COSY (<sup>1</sup>H-<sup>1</sup>H), HMQC (<sup>1</sup>H–<sup>13</sup>C), and HMBC (<sup>1</sup>H–<sup>13</sup>C) two-dimensional NMR spectroscopy methods.<sup>1</sup>H, and <sup>13</sup>C NMR spectroscopy were used to investigate all the prepared derivatives. The acute toxicity of the aforementioned compounds was preliminarily evaluated using a specially developed Toxicity Assessment Software Tool within the United States Environmental Protection Agency. The LD<sub>50</sub> values for rats following oral administration of the compounds tested by the QSAR method. According to the projected toxicological effects, compounds (<b>II</b>), (<b>III</b>) can be classified into Class 4 in terms of toxicity. Compounds (<b>IV</b>), (<b>V</b>) and (<b>VI</b>) have low toxicity and very low toxicity, respectively. <b>Conclusions:</b> The anti-inflammatory activity of the synthesized hydrazones has been evaluated and it has been demonstrated that these compounds were ineffective in comparison with ibuprofen at a dosage of 100 mg/kg (<i>p</i><sup>2</sup> < 0.05). The low toxicity level of all the tested compounds was predicted by the computer modeling. The LD<sub>50</sub> values of the compounds range from 445.461 to 1491.991 mg/kg. The studies on the model of formalin paw edema in nonlinear white rats indicate the absence of an anti-inflammatory effect of the tested compounds.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 5","pages":"2066 - 2075"},"PeriodicalIF":1.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142410946","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}
Pub Date : 2024-10-09DOI: 10.1134/S1068162024050352
О. V. Gribovskaya, V. V. Yanchenko, A. M. Tsygankov, V. P. Martinovich
Objective: Тhe development of new proteins against COVID-19 is an urgent task. The goal of this work was the synthesis of the peptides Lys-Ile-Ala-Asp-Tyr-Asn-Tyr-Lys-Leu (417–425 aa) and Val-Arg-Gln-Ala-Pro-Asn-Gly- Gln-Thr (407–415 aa) – fragments of the surface glycoprotein Spike of SARS-CoV-2 – as potential components of a vaccine against COVID-19 and the study of their binding to human blood cells. Methods: The compounds were synthesized using peptide chemistry methods in solution. The effect of peptides on leukocytes was studied by flow cytometry using monoclonal antibodies against molecules expressed on leukocytes (CD45), that are responsible for the early activation of lymphocytes (CD69) and basophils (CD203c, CD63). The concentration of IFN-γ, which was secreted by lymphocytes in response to peptides, was determined by ELISA. Results and Discussion: It was established that peptides could bind to leukocytes, which indicates the universality of reactions to peptides, especially in innate immune cells. It was shown that the Lys-Ile-Ala-Asp-Tyr-Asn-Tyr-Lys-Leu peptide contacted the leukocytes activated the lymphocytes and basophils. It was confirmed by an increase in gamma interferon compared to the Val-Arg-Gln-Ala-Pro-Asn-Gly-Gln-Thr. Conclusions: A method that allows to evaluate the effect of short peptides on leukocytes was tested. It was shown that the obtained peptides interact with leukocytes, activating them, which was evidenced by secretion of IFN-γ. Our proposed method for evaluating the effect of short peptides on blood cells is the first step in the development of a new peptide-based vaccine against COVID-19.
{"title":"Synthesis of SARS-CoV-2 Spike Glycoprotein Peptide Fragments and Study of Their Binding to Human Blood Cells","authors":"О. V. Gribovskaya, V. V. Yanchenko, A. M. Tsygankov, V. P. Martinovich","doi":"10.1134/S1068162024050352","DOIUrl":"10.1134/S1068162024050352","url":null,"abstract":"<p><b>Objective:</b> Тhe development of new proteins against COVID-19 is an urgent task. The goal of this work was the synthesis of the peptides Lys-Ile-Ala-Asp-Tyr-Asn-Tyr-Lys-Leu (417–425 aa) and Val-Arg-Gln-Ala-Pro-Asn-Gly- Gln-Thr (407–415 aa) – fragments of the surface glycoprotein Spike of SARS-CoV-2 – as potential components of a vaccine against COVID-19 and the study of their binding to human blood cells. <b>Methods:</b> The compounds were synthesized using peptide chemistry methods in solution. The effect of peptides on leukocytes was studied by flow cytometry using monoclonal antibodies against molecules expressed on leukocytes (CD45), that are responsible for the early activation of lymphocytes (CD69) and basophils (CD203c, CD63). The concentration of IFN-γ, which was secreted by lymphocytes in response to peptides, was determined by ELISA. <b>Results and Discussion:</b> It was established that peptides could bind to leukocytes, which indicates the universality of reactions to peptides, especially in innate immune cells. It was shown that the Lys-Ile-Ala-Asp-Tyr-Asn-Tyr-Lys-Leu peptide contacted the leukocytes activated the lymphocytes and basophils. It was confirmed by an increase in gamma interferon compared to the Val-Arg-Gln-Ala-Pro-Asn-Gly-Gln-Thr. <b>Conclusions:</b> A method that allows to evaluate the effect of short peptides on leukocytes was tested. It was shown that the obtained peptides interact with leukocytes, activating them, which was evidenced by secretion of IFN-γ. Our proposed method for evaluating the effect of short peptides on blood cells is the first step in the development of a new peptide-based vaccine against COVID-19.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 5","pages":"1904 - 1916"},"PeriodicalIF":1.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142410903","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}
Pub Date : 2024-10-09DOI: 10.1134/S1068162024050297
V. N. Azev, L. G. Mustaeva, E. Yu. Gorbunova, L. K. Baidakova, A. N. Chulin, L. N. Maslov, A. V. Mukhomedzyanov, М. В. Molchanov, A. I. Miroshnikov
Objective: The disadvantages of the published methods for the preparation of peptide deltorphin II and its analogues hamper thorough biological investigations of this class of molecules. Aiming to develop a more productive synthetic method we investigated an approach where Boc/Bzl solid phase peptide synthesis technique was employed without the utilization of anhydrous hydrogen fluoride. Deltorphin II and its analogues were prepared in high yields and purity using the developed method and trifluoromethane sulfonic acid as a deprotection regent. Methods: Boc/Bzl solid phase peptide synthesis using accelerated and classical coulpling protocols was employed. A few strong Lewis acids were used in the final deprotection synthesis step. Results and Discussion: The toxicity and aggressive nature of hydrogen fluoride have resulted in the development of alternative strong Lewis acid-based reagents for the final deprotection and cleavage steps in Boc/Bzl peptide synthesis. Unlike hydrogen fluoride, these acids have high boiling points; however, the favorable physicochemical properties of most peptides allow them to be quite easily isolated from the cleavage cocktails by precipitation with ether. We found that this simple procedure is not suitable for the isolation of deltorphin II peptide and its analogs and developed and successfully implemented alternative methods of synthesis, isolation, and purification of these peptides. Conclusions: The use of strong Lewis acids as an alternative to anhydrous hydrogen fluoride may complicate the isolation of hydrophobic peptides by the standard techniques. An alternative method was proposed and successfully employed in the preparation of peptide deltorphin II and its three analogs. The developed procedures can be used to purify other hydrophobic peptides.
研究目的已公布的多肽 deltorphin II 及其类似物的制备方法存在很多缺点,妨碍了对这类分子进行深入的生物学研究。为了开发一种更有效的合成方法,我们研究了一种不使用无水氟化氢的 Boc/Bzl 固相肽合成技术。使用所开发的方法和三氟甲烷磺酸作为脱保护剂,制备出了高产率和高纯度的 Deltorphin II 及其类似物。制备方法采用 Boc/Bzl 固相多肽合成法,使用加速和经典耦合方案。在最后的脱保护合成步骤中使用了一些强路易斯酸。结果与讨论:由于氟化氢的毒性和侵蚀性,人们开发了基于强路易斯酸的替代试剂,用于 Boc/Bzl 多肽合成的最后脱保护和裂解步骤。与氟化氢不同,这些酸的沸点较高;不过,由于大多数肽具有良好的物理化学特性,因此很容易通过乙醚沉淀将它们从裂解鸡尾酒中分离出来。我们发现这种简单的方法并不适用于分离 deltorphin II 肽及其类似物,因此开发并成功实施了合成、分离和纯化这些肽的替代方法。结论使用强路易斯酸替代无水氟化氢可能会使标准技术分离疏水性多肽的过程复杂化。我们提出了一种替代方法,并成功用于制备多肽 deltorphin II 及其三种类似物。所开发的程序可用于纯化其他疏水性多肽。
{"title":"Boc/Bzl Solid-Phase Synthesis of Deltorphin II and Its Analogs without the Utilization of Anhydrous Hydrogen Fluoride","authors":"V. N. Azev, L. G. Mustaeva, E. Yu. Gorbunova, L. K. Baidakova, A. N. Chulin, L. N. Maslov, A. V. Mukhomedzyanov, М. В. Molchanov, A. I. Miroshnikov","doi":"10.1134/S1068162024050297","DOIUrl":"10.1134/S1068162024050297","url":null,"abstract":"<p><b>Objective:</b> The disadvantages of the published methods for the preparation of peptide deltorphin II and its analogues hamper thorough biological investigations of this class of molecules. Aiming to develop a more productive synthetic method we investigated an approach where Boc/Bzl solid phase peptide synthesis technique was employed without the utilization of anhydrous hydrogen fluoride. Deltorphin II and its analogues were prepared in high yields and purity using the developed method and trifluoromethane sulfonic acid as a deprotection regent. <b>Methods:</b> Boc/Bzl solid phase peptide synthesis using accelerated and classical coulpling protocols was employed. A few strong Lewis acids were used in the final deprotection synthesis step. <b>Results and Discussion:</b> The toxicity and aggressive nature of hydrogen fluoride have resulted in the development of alternative strong Lewis acid-based reagents for the final deprotection and cleavage steps in Boc/Bzl peptide synthesis. Unlike hydrogen fluoride, these acids have high boiling points; however, the favorable physicochemical properties of most peptides allow them to be quite easily isolated from the cleavage cocktails by precipitation with ether. We found that this simple procedure is not suitable for the isolation of deltorphin II peptide and its analogs and developed and successfully implemented alternative methods of synthesis, isolation, and purification of these peptides. <b>Conclusions:</b> The use of strong Lewis acids as an alternative to anhydrous hydrogen fluoride may complicate the isolation of hydrophobic peptides by the standard techniques. An alternative method was proposed and successfully employed in the preparation of peptide deltorphin II and its three analogs. The developed procedures can be used to purify other hydrophobic peptides.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 5","pages":"1701 - 1709"},"PeriodicalIF":1.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142410876","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}
Pub Date : 2024-10-09DOI: 10.1134/S1068162024050029
Munir Ur Rehman, Aftab Alam, Syed Adnan Ali Shah, Abid Ali, Qaisar Ali, Abdullah F. AlAsmari, Fawaz Alasmari, Momin Khan
Objective: The aim of this study was to synthesize azine analogues of 1,2-diphenylethan-1-one while assessing their ability to scavenge free radicals with DPPH. In order to explore these compounds’ potential as novel antioxidant agents with possible applications in the pharmaceutical, neutraceutical, and other industries, we synthesized them. Methods: The initial steps involved reacting 1,2-diphenylethan-1-one and additional amount of hydrated hydrazine in an ethanol solvent to produce the needed hydrazone, which paved the way for a two-step reaction that produced azine derivatives. Ultimately, a number of substituted aldehydes that are aromatic were heated by reflux condition, catalyzed by acetic acid with the obtained hydrazone to produce the azine derivatives in high yields. Results: These synthetic derivatives were screened for their anti-oxidant activity, compound (IIe) (IC50 = 24.13 ± 0.27 µM), (IIf) (IC50 = 29.11 ± 0.41 µM), and (IIg) (IC50 = 31.12 ± 0.44 µM) attributed the most excellent activity, however compound (IIc) and (IId) were found as significant DPPH free radical scavenging agents with IC50 values 46.21 ± 0.12 and 49.23 ± 0.54 µM, respectively while compound (IIa) and (IIb) displayed less anti-oxidant effect with IC50 values 55.11 ± 0.24 and 66.21 ± 0.12 µM. Conclusions: The study shows that the azine derivatives under investigation have promising potential as synthetic antioxidants due to their significant DPPH radical scavenging action. Furthermore, compounds containing electron-donating groups exhibit antioxidant activity comparable to that of ascorbic acid, an antioxidant that occurs naturally. These findings highlight the antioxidant qualities of the synthetic azine derivatives and suggest potential applications as medical treatments for oxidative stress-related illnesses.
{"title":"Discovering the DPPH Free Radical Scavenging Activity of Azine Derivatives Bearing Ethyl Phenyl Ketone Moiety","authors":"Munir Ur Rehman, Aftab Alam, Syed Adnan Ali Shah, Abid Ali, Qaisar Ali, Abdullah F. AlAsmari, Fawaz Alasmari, Momin Khan","doi":"10.1134/S1068162024050029","DOIUrl":"10.1134/S1068162024050029","url":null,"abstract":"<p><b>Objective:</b> The aim of this study was to synthesize azine analogues of 1,2-diphenylethan-1-one while assessing their ability to scavenge free radicals with DPPH. In order to explore these compounds’ potential as novel antioxidant agents with possible applications in the pharmaceutical, neutraceutical, and other industries, we synthesized them. <b>Methods:</b> The initial steps involved reacting 1,2-diphenylethan-1-one and additional amount of hydrated hydrazine in an ethanol solvent to produce the needed hydrazone, which paved the way for a two-step reaction that produced azine derivatives. Ultimately, a number of substituted aldehydes that are aromatic were heated by reflux condition, catalyzed by acetic acid with the obtained hydrazone to produce the azine derivatives in high yields. <b>Results:</b> These synthetic derivatives were screened for their anti-oxidant activity, compound (<b>IIe</b>) (IC<sub>50</sub> = 24.13 ± 0.27 µM), (<b>IIf</b>) (IC<sub>50</sub> = 29.11 ± 0.41 µM), and (<b>IIg</b>) (IC<sub>50</sub> = 31.12 ± 0.44 µM) attributed the most excellent activity, however compound (<b>IIc</b>) and (<b>IId</b>) were found as significant DPPH free radical scavenging agents with IC<sub>50</sub> values 46.21 ± 0.12 and 49.23 ± 0.54 µM, respectively while compound (<b>IIa</b>) and (<b>IIb</b>) displayed less anti-oxidant effect with IC<sub>50</sub> values 55.11 ± 0.24 and 66.21 ± 0.12 µM. <b>Conclusions:</b> The study shows that the azine derivatives under investigation have promising potential as synthetic antioxidants due to their significant DPPH radical scavenging action. Furthermore, compounds containing electron-donating groups exhibit antioxidant activity comparable to that of ascorbic acid, an antioxidant that occurs naturally. These findings highlight the antioxidant qualities of the synthetic azine derivatives and suggest potential applications as medical treatments for oxidative stress-related illnesses.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 5","pages":"1639 - 1645"},"PeriodicalIF":1.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142410877","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}
Objective: The objective of this study was to design and synthesize novel apigenin derivatives and evaluate their antitumor activities against NSCLC cells. Methods: A series of apigenin derivatives were synthesized and their antiproliferative effects were evaluated against the NSCLC cell line A549. The most promising compounds were identified based on their antitumor activities. Their safety was confirmed by testing them on the normal human lung cell line Beas-2B. The mechanisms of their antitumor activities were investigated by inducing apoptosis in A549 cells and inhibiting Akt protein phosphorylation. The physicochemical and ADME properties of these compounds were also predicted to evaluate their potential as PI3K inhibitors for NSCLC therapy. Results and Discussion: Compounds (Va) and (VIa) exhibited suitable antitumor activities against A549 cells, with no significant toxicity towards Beas-2B cells. They were capable of inducing apoptosis in A549 cells and inhibiting Akt protein phosphorylation, which preliminarily revealed their mechanisms for antitumor activities in vitro. The predictions of physicochemical and ADME properties showed that compound (VIa) would be a potent PI3K inhibitor for NSCLC therapy in the future. Conclusions: This study has successfully designed and synthesized apigenin derivatives with antitumor activities for NSCLC therapy. Compounds (Va) and (VIa) exhibited suitable antitumor activities with low toxicity and promising mechanisms of action. The physicochemical and ADME properties of compound (VIa) suggest its potential as a potent PI3K inhibitor for NSCLC therapy in the future. These findings provide valuable insights for the development of novel therapeutic agents against NSCLC.
{"title":"Design, Synthesis, and Biological Evaluation of Novel Apigenin Derivatives as Potential Antitumor Agents","authors":"Bei-Qiao He, Xiao-Xiao Fan, Tian-Yu Zheng, Ya-Ting Gao, Xu Chen, Yong-Gang Liu, Yuan-Yuan Zhang","doi":"10.1134/S1068162024050091","DOIUrl":"10.1134/S1068162024050091","url":null,"abstract":"<p><b>Objective:</b> The objective of this study was to design and synthesize novel apigenin derivatives and evaluate their antitumor activities against NSCLC cells. <b>Methods:</b> A series of apigenin derivatives were synthesized and their antiproliferative effects were evaluated against the NSCLC cell line A549. The most promising compounds were identified based on their antitumor activities. Their safety was confirmed by testing them on the normal human lung cell line Beas-2B. The mechanisms of their antitumor activities were investigated by inducing apoptosis in A549 cells and inhibiting Akt protein phosphorylation. The physicochemical and ADME properties of these compounds were also predicted to evaluate their potential as PI3K inhibitors for NSCLC therapy. <b>Results and Discussion:</b> Compounds (<b>Va</b>) and (<b>VIa</b>) exhibited suitable antitumor activities against A549 cells, with no significant toxicity towards Beas-2B cells. They were capable of inducing apoptosis in A549 cells and inhibiting Akt protein phosphorylation, which preliminarily revealed their mechanisms for antitumor activities in vitro. The predictions of physicochemical and ADME properties showed that compound (<b>VIa</b>) would be a potent PI3K inhibitor for NSCLC therapy in the future. <b>Conclusions:</b> This study has successfully designed and synthesized apigenin derivatives with antitumor activities for NSCLC therapy. Compounds (<b>Va</b>) and (<b>VIa</b>) exhibited suitable antitumor activities with low toxicity and promising mechanisms of action. The physicochemical and ADME properties of compound (<b>VIa</b>) suggest its potential as a potent PI3K inhibitor for NSCLC therapy in the future. These findings provide valuable insights for the development of novel therapeutic agents against NSCLC.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 5","pages":"1659 - 1671"},"PeriodicalIF":1.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142410901","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}
Pub Date : 2024-10-09DOI: 10.1134/S1068162024050066
Rui Li, Ya-Min Ding, Tian Qin, Xuan-Yi Xue, Wei-Wei Liu, Rong-Bin Wei, Yuan-Fen Zhai, Gang Ding, Da-Hua Shi
Objective: In search of the better anticancer agents, fifteen bakuchiol-1,3,5-triazine derivatives were designed and synthesized through nucleophilic substitution reaction. Methods: The newly synthesized derivatives were evaluated for their in vitro cytotoxic activity against Panc-1, MDA-MB-231, A549, and UM-UC-3 using the MTT assay. Results and Discussion: The data revealed that all of the bakuchiol-1,3,5-triazine derivatives could inhibit the proliferation of Panc-1 cells. Four compounds exhibited better antiproliferative activities than that of bakuchiol. Among them, compound (IVj) displayed potent antiproliferative activity with IC50 values of 21.83 μM. Compound (IVj) also showed potent inhibitory activity against the proliferation of MDA-MB-231, A549, and UM-UC-3 cells when compared with bakuchiol. Additionally, compound (IVj) exhibited strong inhibitory effects on the migration, invasion, and adhesion of Panc-1 cells. Conclusions: The results showed that, compound (IVj) could be a promising candidate agent for the treatment of cancer.
{"title":"Design, Synthesis, and Anticancer Activities of Bakuchiol-1,3,5-triazine Derivatives","authors":"Rui Li, Ya-Min Ding, Tian Qin, Xuan-Yi Xue, Wei-Wei Liu, Rong-Bin Wei, Yuan-Fen Zhai, Gang Ding, Da-Hua Shi","doi":"10.1134/S1068162024050066","DOIUrl":"10.1134/S1068162024050066","url":null,"abstract":"<p><b>Objective:</b> In search of the better anticancer agents, fifteen bakuchiol-1,3,5-triazine derivatives were designed and synthesized through nucleophilic substitution reaction. <b>Methods:</b> The newly synthesized derivatives were evaluated for their <i>in vitro</i> cytotoxic activity against Panc-1, MDA-MB-231, A549, and UM-UC-3 using the MTT assay. <b>Results and Discussion:</b> The data revealed that all of the bakuchiol-1,3,5-triazine derivatives could inhibit the proliferation of Panc-1 cells. Four compounds exhibited better antiproliferative activities than that of bakuchiol. Among them, compound (<b>IVj</b>) displayed potent antiproliferative activity with IC<sub>50</sub> values of 21.83 μM. Compound (<b>IVj</b>) also showed potent inhibitory activity against the proliferation of MDA-MB-231, A549, and UM-UC-3 cells when compared with bakuchiol. Additionally, compound (<b>IVj</b>) exhibited strong inhibitory effects on the migration, invasion, and adhesion of Panc-1 cells. <b>Conclusions:</b> The results showed that, compound (<b>IVj</b>) could be a promising candidate agent for the treatment of cancer.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 5","pages":"1851 - 1862"},"PeriodicalIF":1.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142410906","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}