Pub Date : 2020-11-23DOI: 10.2174/2212796814999201123194016
Ahmed Etman, Sherif S. Abdel Mageed, M. Ali, Mahmoud A. El Hassab
Cyclin-Dependent Kinases (CDKs) are a family of enzymes that, along with their Cyclin partners, play a crucial role in cell cycle regulation at many biological functions such as proliferation, differentiation, DNA repair, and apoptosis. Thus, they are tightly regulated by a number of inhibitory and activating enzymes. Deregulation of these kinases’ activity either by amplification, overexpression or mutation of CDKs or Cyclins leads to uncontrolled proliferation of cancer cells. Hyperactivity of these kinases has been reported in a wide variety of human cancers. Hence, CDKs have been established as one of the most attractive pharmacological targets in the development of promising anticancer drugs. The elucidated structural features and the well-characterized molecular mechanisms of CDKs have been the guide in designing inhibitors to these kinases. Yet, they remain a challenging therapeutic class as they share conserved structure similarity in their active site. Several inhibitors have been discovered from natural sources or identified through high throughput screening and rational drug design approaches. Most of these inhibitors target the ATP binding pocket, therefore, they suffer from a number of limitations. Here, a growing number of ATP noncompetitive peptides and small molecules has been reported.
{"title":"Cyclin-Dependent Kinase as a Novel Therapeutic Target: An Endless Story","authors":"Ahmed Etman, Sherif S. Abdel Mageed, M. Ali, Mahmoud A. El Hassab","doi":"10.2174/2212796814999201123194016","DOIUrl":"https://doi.org/10.2174/2212796814999201123194016","url":null,"abstract":"\u0000\u0000Cyclin-Dependent Kinases (CDKs) are a family of enzymes that, along with their Cyclin\u0000partners, play a crucial role in cell cycle regulation at many biological functions such as proliferation,\u0000differentiation, DNA repair, and apoptosis. Thus, they are tightly regulated by a number of inhibitory\u0000and activating enzymes. Deregulation of these kinases’ activity either by amplification,\u0000overexpression or mutation of CDKs or Cyclins leads to uncontrolled proliferation of cancer cells.\u0000Hyperactivity of these kinases has been reported in a wide variety of human cancers. Hence, CDKs\u0000have been established as one of the most attractive pharmacological targets in the development of\u0000promising anticancer drugs. The elucidated structural features and the well-characterized molecular\u0000mechanisms of CDKs have been the guide in designing inhibitors to these kinases. Yet, they remain\u0000a challenging therapeutic class as they share conserved structure similarity in their active site.\u0000Several inhibitors have been discovered from natural sources or identified through high throughput\u0000screening and rational drug design approaches. Most of these inhibitors target the ATP binding\u0000pocket, therefore, they suffer from a number of limitations. Here, a growing number of ATP noncompetitive\u0000peptides and small molecules has been reported.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83918006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-11-19DOI: 10.2174/2212796814999200604121937
Mateen A. Khan
Cellular iron uptake, utilization, and storage are tightly controlled through the action of iron regulatory proteins (IRPs). IRPs achieve this control by binding to IREs-mRNA in the 5'- or 3'-end of mRNAs that encode proteins involved in iron metabolism. The interaction of iron regulatory proteins with mRNAs containing an iron responsive element plays a central role in this regulation. The IRE RNA family of mRNA regulatory structures combines absolutely conserved protein binding sites with phylogenetically conserved base pairs that are specific to each IREs and influence RNA/protein stability. Our previous result revealed the binding and kinetics of IRE RNA with IRP1. The aim of the present study is to gain further insight into the differences in protein/RNA stability as a function of pH and ionic strength. To determine the extent to which the binding affinity and stability of protein/RNA complex was affected by ionic strength and pH. Fluorescence spectroscopy was used to characterize IRE RNA-IRP protein interaction. Scatchard analysis revealed that the IRP1 protein binds to a single IRE RNA molecule. The binding affinity of two IRE RNA/IRP was significantly changed with the change in pH. The data suggests that the optimum binding of RNA/IRP complex occurred at pH 7.6. Dissociation constant for two IRE RNA/IRP increased with an increase in ionic strength, with a larger effect for FRT IRE RNA. This suggests that numerous electrostatic interactions occur in the ferritin IRE RNA/IRP than ACO2 IRE RNA/IRP complex. Iodide quenching shows that the majority of the tryptophan residues in IRP1 are solvent-accessible, assuming that most of the tryptophan residues contribute to protein fluorescence. The results obtained from this study clearly indicate that IRE RNA/IRP complex is destabilized by the change in pH and ionic strength. These observations suggest that both pH and ion are important for the assembly and stability of the IRE RNA/IRP complex formation.
{"title":"Analysis of Ion and pH Effects on Iron Response Element (IRE) and mRNA-Iron Regulatory Protein (IRP1) Interactions","authors":"Mateen A. Khan","doi":"10.2174/2212796814999200604121937","DOIUrl":"https://doi.org/10.2174/2212796814999200604121937","url":null,"abstract":"\u0000\u0000Cellular iron uptake, utilization, and storage are tightly controlled\u0000through the action of iron regulatory proteins (IRPs). IRPs achieve this control by binding to\u0000IREs-mRNA in the 5'- or 3'-end of mRNAs that encode proteins involved in iron metabolism.\u0000The interaction of iron regulatory proteins with mRNAs containing an iron responsive\u0000element plays a central role in this regulation. The IRE RNA family of mRNA regulatory\u0000structures combines absolutely conserved protein binding sites with phylogenetically conserved\u0000base pairs that are specific to each IREs and influence RNA/protein stability. Our\u0000previous result revealed the binding and kinetics of IRE RNA with IRP1. The aim of the present\u0000study is to gain further insight into the differences in protein/RNA stability as a function\u0000of pH and ionic strength.\u0000\u0000\u0000\u0000To determine the extent to which the binding affinity and stability of protein/RNA\u0000complex was affected by ionic strength and pH.\u0000\u0000\u0000\u0000Fluorescence spectroscopy was used to characterize IRE RNA-IRP protein interaction.\u0000\u0000\u0000\u0000Scatchard analysis revealed that the IRP1 protein binds to a single IRE RNA molecule.\u0000The binding affinity of two IRE RNA/IRP was significantly changed with the change in\u0000pH. The data suggests that the optimum binding of RNA/IRP complex occurred at pH 7.6.\u0000Dissociation constant for two IRE RNA/IRP increased with an increase in ionic strength,\u0000with a larger effect for FRT IRE RNA. This suggests that numerous electrostatic interactions\u0000occur in the ferritin IRE RNA/IRP than ACO2 IRE RNA/IRP complex. Iodide quenching\u0000shows that the majority of the tryptophan residues in IRP1 are solvent-accessible, assuming\u0000that most of the tryptophan residues contribute to protein fluorescence.\u0000\u0000\u0000\u0000The results obtained from this study clearly indicate that IRE RNA/IRP complex\u0000is destabilized by the change in pH and ionic strength. These observations suggest that\u0000both pH and ion are important for the assembly and stability of the IRE RNA/IRP complex\u0000formation.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"19 1","pages":"88-99"},"PeriodicalIF":0.0,"publicationDate":"2020-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78401406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-11-19DOI: 10.2174/2212796814666200406100247
R. Rathour, Vaishali Sharma, Nidhi Rana, R. Bhatia, A. Bhatt
Microbial degradation of highly stable textile dyes, using lignin peroxidase, is an eco-friendly, less expensive and much advantageous in comparison to the chemical method. Biodegradation potential of lignin peroxidase (LiP), from Pseudomonas fluorescens LiP-RL5, was enhanced after optimization and purification so as to use it as a potential bioresource for the treatment of textile effluent. LiP producing bacterial isolate was primarily screened by methylene blue assay followed by LiP assay. The standard protocol was used for purification of lignin peroxidase and purified LiP was finally used for degradation of textile dyes. 57 bacterial isolates were screened for lignin peroxidase activity. Isolate LiP-RL5 showed maximum activity (19.8 ±0.33 %) in terms of methylene blue reduction in comparison to others. Biochemical and molecular characterization of LiP-RL5 showed 99 % similarity with P. fluorescens. Lignin peroxidase activity was increased by 50 % after optimization of cultural conditions. Maximum enhancement in the activity was achieved when peptone was used as a nitrogen source. LiP from P. fluorescens LiP-RL5 was further purified up to 2 folds. SDS-PAGE analysis revealed a single protein band of approximately 40 kDa. Enzyme also showed high catalytic efficiency with Km= 6.94 mM and Vmax= 78.74 μmol/ml/min. Purified enzyme was able to decolorize the simulated textile effluent up to 45.05 ±0.28 % after 40 minutes. : High catalytic efficiency of purified LiP from P. fluorescens LiP-RL5 suggests its utility as a potential candidate for biodegradation of toxic dyes in the industrial effluent, which could be successfully utilized for wastewater treatment at commercial level.
{"title":"Bioremediation of Simulated Textile Effluent by an Efficient Bio-catalyst Purified from a Novel Pseudomonas fluorescence LiP-RL5","authors":"R. Rathour, Vaishali Sharma, Nidhi Rana, R. Bhatia, A. Bhatt","doi":"10.2174/2212796814666200406100247","DOIUrl":"https://doi.org/10.2174/2212796814666200406100247","url":null,"abstract":"\u0000\u0000Microbial degradation of highly stable textile dyes, using lignin peroxidase,\u0000is an eco-friendly, less expensive and much advantageous in comparison to the\u0000chemical method.\u0000\u0000\u0000\u0000Biodegradation potential of lignin peroxidase (LiP), from Pseudomonas fluorescens\u0000LiP-RL5, was enhanced after optimization and purification so as to use it as a potential\u0000bioresource for the treatment of textile effluent.\u0000\u0000\u0000\u0000 LiP producing bacterial isolate was primarily screened by methylene blue assay\u0000followed by LiP assay. The standard protocol was used for purification of lignin peroxidase\u0000and purified LiP was finally used for degradation of textile dyes.\u0000\u0000\u0000\u000057 bacterial isolates were screened for lignin peroxidase activity. Isolate LiP-RL5\u0000showed maximum activity (19.8 ±0.33 %) in terms of methylene blue reduction in comparison\u0000to others. Biochemical and molecular characterization of LiP-RL5 showed 99 % similarity\u0000with P. fluorescens. Lignin peroxidase activity was increased by 50 % after optimization\u0000of cultural conditions. Maximum enhancement in the activity was achieved when peptone\u0000was used as a nitrogen source. LiP from P. fluorescens LiP-RL5 was further purified up to 2\u0000folds. SDS-PAGE analysis revealed a single protein band of approximately 40 kDa. Enzyme\u0000also showed high catalytic efficiency with Km= 6.94 mM and Vmax= 78.74 μmol/ml/min. Purified\u0000enzyme was able to decolorize the simulated textile effluent up to 45.05 ±0.28 % after\u000040 minutes.\u0000\u0000\u0000\u0000: High catalytic efficiency of purified LiP from P. fluorescens LiP-RL5 suggests\u0000its utility as a potential candidate for biodegradation of toxic dyes in the industrial effluent,\u0000which could be successfully utilized for wastewater treatment at commercial level.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"32 1","pages":"128-139"},"PeriodicalIF":0.0,"publicationDate":"2020-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87668789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-11-19DOI: 10.2174/2212796814666200520083818
I. Uchendu, H. Okoroiwu
Prevalence of chemical-induced renal injuries has been on a fast rise over the years and has become the leading cause of mortality and morbidity in the society, with environmental pollutants, heavy metals inclusive, seen as the causal agents. Recently, the role of medicinal foods in human health has gained considerable attention. We investigated the protective effects of methanolic extract of Nigella sativa (MENS) (Black seed) against cadmium-induced renal toxicity in albino rats. Twenty-five (25) male albino rats, weighing (150-170g), were randomly grouped into five groups: A-E. Group B (Negative Control) received intraperitoneal administration of cadmium chloride (CdCl2, 5mg/kg) only, group C received CdCl2 and low dose MENS (300mg/kg, oral), group D received CdCl2 and high dose MENS (600mg/kg, oral), group E (Positive control) received CdCl2 and Vitamin C (200mg/kg, oral), for 7 days. No treatment was administered to group A (Normal control). Renal injury was assessed by measuring serum levels of Na+, K+, creatinine and blood urea nitrogen (BUN) using standard methods. The kidneys were harvested for histopathological examination. CdCl2 induced significant nephrotoxicity with marked elevation in the levels of biochemical markers of renal functions (p<0.05 or p<0.01); these were, however, ameliorated by a low dose of MENS. Histopathological examination of the kidney sections supported the biochemical findings. We conclude that Nigella sativa seed extract, at a low dose, is potentially nephroprotective against harmful chemical toxins such as cadmium.
{"title":"Nigella sativa Seed Protects Against Cadmium-induced Renal Toxicity in Rats","authors":"I. Uchendu, H. Okoroiwu","doi":"10.2174/2212796814666200520083818","DOIUrl":"https://doi.org/10.2174/2212796814666200520083818","url":null,"abstract":"\u0000\u0000Prevalence of chemical-induced renal injuries has been on a fast rise\u0000over the years and has become the leading cause of mortality and morbidity in the society,\u0000with environmental pollutants, heavy metals inclusive, seen as the causal agents. Recently,\u0000the role of medicinal foods in human health has gained considerable attention.\u0000\u0000\u0000\u0000We investigated the protective effects of methanolic extract of Nigella sativa\u0000(MENS) (Black seed) against cadmium-induced renal toxicity in albino rats.\u0000\u0000\u0000\u0000Twenty-five (25) male albino rats, weighing (150-170g), were randomly grouped\u0000into five groups: A-E. Group B (Negative Control) received intraperitoneal administration of\u0000cadmium chloride (CdCl2, 5mg/kg) only, group C received CdCl2 and low dose MENS\u0000(300mg/kg, oral), group D received CdCl2 and high dose MENS (600mg/kg, oral), group E\u0000(Positive control) received CdCl2 and Vitamin C (200mg/kg, oral), for 7 days. No treatment\u0000was administered to group A (Normal control). Renal injury was assessed by measuring serum\u0000levels of Na+, K+, creatinine and blood urea nitrogen (BUN) using standard methods.\u0000The kidneys were harvested for histopathological examination.\u0000\u0000\u0000\u0000CdCl2 induced significant nephrotoxicity with marked elevation in the levels of biochemical\u0000markers of renal functions (p<0.05 or p<0.01); these were, however, ameliorated\u0000by a low dose of MENS. Histopathological examination of the kidney sections supported the\u0000biochemical findings.\u0000\u0000\u0000\u0000We conclude that Nigella sativa seed extract, at a low dose, is potentially nephroprotective\u0000against harmful chemical toxins such as cadmium.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"6 1","pages":"140-149"},"PeriodicalIF":0.0,"publicationDate":"2020-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83152212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-11-19DOI: 10.2174/2212796814999200801020729
T. Fatoki
This study aimed at discovering chemiluminescent analogues of luminol, predict their molecular binding to hemoglobin of bloodstains in household crime, and expound the mechanism of chemiluminescence of luminol. Similarity and clustering analyses of luminol analogues were conducted, and molecular docking was carried out using hemoglobin from Homo sapiens and four domestic organisms namely Gallus gallus, Drosophila melanogaster, Rattus norvegicus, and Canis familiaris. The results showed the order of overall binding score as D. melanogaster > H. sapiens > C. familiaris > R. norvegicus > G. gallus. Seven compounds namely ZINC16958228, ZINC17023010, ZINC19915427, ZINC34928954, ZINC19915369, ZINC19915444, and ZINC82294978, were found to be consistently stable in binding with diverse hemoglobin and possibly have chemiluminescence than luminol in this in silico study. The interaction of human hemoglobin with luminol and its analogues, showed that amino acid residues His45, Lys61, Asn68, Val73, Met76, Pro77, Ala79, Ala82, Leu83, Pro95, Phe98, Lys99, Ser102, Ser133, Ala134, and Thr134, were possibly significant in the mechanism of action of presumptive test compounds. It was hypothesized that the improved mechanism of chemiluminescent for the identification of blood was based on peroxidase-like reaction, that produces nitric oxide which binds to hemoglobin (Hb) and inhibits Hb degradation without yielding fluorescent products. The compound 2,3-benzodioxine-1,4,5(6H)-trione was formed, which possibly emits light. This study provides novel insight on the luminol and its expanded mechanism for broader possible applications with careful development of new methodologies.
{"title":"In Silico Investigation of Luminol, Its Analogues and Mechanism of Chemiluminescence for Blood Identification Beyond Forensics","authors":"T. Fatoki","doi":"10.2174/2212796814999200801020729","DOIUrl":"https://doi.org/10.2174/2212796814999200801020729","url":null,"abstract":"\u0000\u0000This study aimed at discovering chemiluminescent analogues of luminol,\u0000predict their molecular binding to hemoglobin of bloodstains in household crime, and\u0000expound the mechanism of chemiluminescence of luminol.\u0000\u0000\u0000\u0000Similarity and clustering analyses of luminol analogues were conducted,\u0000and molecular docking was carried out using hemoglobin from Homo sapiens and\u0000four domestic organisms namely Gallus gallus, Drosophila melanogaster, Rattus norvegicus,\u0000and Canis familiaris.\u0000\u0000\u0000\u0000The results showed the order of overall binding score as D. melanogaster > H.\u0000sapiens > C. familiaris > R. norvegicus > G. gallus. Seven compounds namely\u0000ZINC16958228, ZINC17023010, ZINC19915427, ZINC34928954, ZINC19915369,\u0000ZINC19915444, and ZINC82294978, were found to be consistently stable in binding with\u0000diverse hemoglobin and possibly have chemiluminescence than luminol in this in silico\u0000study. The interaction of human hemoglobin with luminol and its analogues, showed that\u0000amino acid residues His45, Lys61, Asn68, Val73, Met76, Pro77, Ala79, Ala82, Leu83,\u0000Pro95, Phe98, Lys99, Ser102, Ser133, Ala134, and Thr134, were possibly significant in the\u0000mechanism of action of presumptive test compounds. It was hypothesized that the improved\u0000mechanism of chemiluminescent for the identification of blood was based on peroxidase-like\u0000reaction, that produces nitric oxide which binds to hemoglobin (Hb) and inhibits Hb degradation\u0000without yielding fluorescent products. The compound 2,3-benzodioxine-1,4,5(6H)-trione\u0000was formed, which possibly emits light.\u0000\u0000\u0000\u0000This study provides novel insight on the luminol and its expanded mechanism\u0000for broader possible applications with careful development of new methodologies.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"61 1","pages":"117-127"},"PeriodicalIF":0.0,"publicationDate":"2020-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87759652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-11-19DOI: 10.2174/2212796814999200818094328
K. Tahmasebi, M. Jafari, F. Izadi, A. Asgari, H. Bahadoran, Javad Heydari, Saeed Khazaie
Exposure to diazinon (DZN) as an organophosphorus insecticide is associated with reducing the antioxidant capacity of cells. N-acetyl cysteine (NAC) is widely used in clinics to treat several diseases related to oxidative stress. The current study was aimed to evaluate the prophylactic and therapeutic roles of NAC on biochemical and oxidative changes induced by acute poisoning of DZN in various tissues of male Wistar rats. Thirty rats were divided into five groups: control group received corn oil as DZN solvent; DZN group received 100 mg/kg of DZN; NAC group received 160 mg/kg of NAC; NAC-DZN and DZN-NAC groups received 160 mg/kg of NAC before and after 100 mg/kg of DZN injection, respectively. Plasma and various tissues were prepared and evaluated for the measurement of the biochemical parameters and oxidative stress biomarkers. Both prophylactic and therapeutic treatments by NAC ameliorated the increased lipid peroxidation and decreased glutathione level and superoxide dismutase, catalase and glutathione S-transferase activities in tissues (P<0.05). Moreover, treatment with the NAC caused a significant reduction in DZN-induced high levels of plasma biochemical parameters. Furthermore, acetylcholinesterase activity was positively correlated with both LDH (P=0.000) activity and GSH (P=0.001) level and negatively correlated with MDA (P=0.009) level in the brain. Results suggest that NAC could effectively ameliorate the DZN-induced oxidative stress and cholinergic hyperactivity in various tissues especially in the brain, through free radicals scavenging and GSH synthesis. Prophylactic approach exerted a stronger protective effect compared to a therapeutic treatment.
{"title":"Evaluation of Prophylactic and Therapeutic Roles of NAcetylcysteine on Biochemical and Oxidative Changes Induced by Acute Poisoning of Diazinon in Various Rat Tissues","authors":"K. Tahmasebi, M. Jafari, F. Izadi, A. Asgari, H. Bahadoran, Javad Heydari, Saeed Khazaie","doi":"10.2174/2212796814999200818094328","DOIUrl":"https://doi.org/10.2174/2212796814999200818094328","url":null,"abstract":"\u0000\u0000Exposure to diazinon (DZN) as an organophosphorus insecticide is\u0000associated with reducing the antioxidant capacity of cells. N-acetyl cysteine (NAC) is widely\u0000used in clinics to treat several diseases related to oxidative stress.\u0000\u0000\u0000\u0000The current study was aimed to evaluate the prophylactic and therapeutic roles of\u0000NAC on biochemical and oxidative changes induced by acute poisoning of DZN in various\u0000tissues of male Wistar rats.\u0000\u0000\u0000\u0000Thirty rats were divided into five groups: control group received corn oil as DZN\u0000solvent; DZN group received 100 mg/kg of DZN; NAC group received 160 mg/kg of NAC;\u0000NAC-DZN and DZN-NAC groups received 160 mg/kg of NAC before and after 100 mg/kg\u0000of DZN injection, respectively. Plasma and various tissues were prepared and evaluated for\u0000the measurement of the biochemical parameters and oxidative stress biomarkers.\u0000\u0000\u0000\u0000Both prophylactic and therapeutic treatments by NAC ameliorated the increased\u0000lipid peroxidation and decreased glutathione level and superoxide dismutase, catalase and\u0000glutathione S-transferase activities in tissues (P<0.05). Moreover, treatment with the NAC\u0000caused a significant reduction in DZN-induced high levels of plasma biochemical parameters.\u0000Furthermore, acetylcholinesterase activity was positively correlated with both LDH\u0000(P=0.000) activity and GSH (P=0.001) level and negatively correlated with MDA (P=0.009)\u0000level in the brain.\u0000\u0000\u0000\u0000 Results suggest that NAC could effectively ameliorate the DZN-induced oxidative\u0000stress and cholinergic hyperactivity in various tissues especially in the brain, through\u0000free radicals scavenging and GSH synthesis. Prophylactic approach exerted a stronger protective\u0000effect compared to a therapeutic treatment.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"34 1","pages":"100-116"},"PeriodicalIF":0.0,"publicationDate":"2020-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82764951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-11-19DOI: 10.2174/2212796814999200807214519
Adarsh Sahu, Preeti Sahu, R. Agrawal
Motivated by evidence garnered from literature probing the use of triazoles in drug discovery and development, we reported the utilization of bioisosteric replacement and molecular hybridization in this review. Bio-isosteric replacement has played a significant role in modulating rapid and versatile strategy in synthesizing molecules with multifaceted medicinal properties. Molecular hybridization seeks to conjugate two molecular fragments with diverse applications under very mild reaction conditions. In this regard, 1,2,3-triazole is a well-known scaffold with widespread occurrence in medicinal compounds. It is characterized to have several bioactivities such as anti-microbial, anti-cancer, anti-viral, analgesic, anti- inflammatory effects. Furthermore, the structural features of 1,2,3-triazoles enable it to mimic different functional groups justifying its use as bio-isostere for the synthesis of new molecules of medicinal interest, which we have reported briefly.
{"title":"A Recent Review on Drug Modification Using 1,2,3-triazole","authors":"Adarsh Sahu, Preeti Sahu, R. Agrawal","doi":"10.2174/2212796814999200807214519","DOIUrl":"https://doi.org/10.2174/2212796814999200807214519","url":null,"abstract":"\u0000\u0000Motivated by evidence garnered from literature probing the use of triazoles in\u0000drug discovery and development, we reported the utilization of bioisosteric replacement and\u0000molecular hybridization in this review. Bio-isosteric replacement has played a significant\u0000role in modulating rapid and versatile strategy in synthesizing molecules with multifaceted\u0000medicinal properties. Molecular hybridization seeks to conjugate two molecular fragments\u0000with diverse applications under very mild reaction conditions. In this regard, 1,2,3-triazole is\u0000a well-known scaffold with widespread occurrence in medicinal compounds. It is characterized\u0000to have several bioactivities such as anti-microbial, anti-cancer, anti-viral, analgesic, anti-\u0000inflammatory effects. Furthermore, the structural features of 1,2,3-triazoles enable it to\u0000mimic different functional groups justifying its use as bio-isostere for the synthesis of new\u0000molecules of medicinal interest, which we have reported briefly.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"109 1","pages":"71-87"},"PeriodicalIF":0.0,"publicationDate":"2020-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74754644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-11-11DOI: 10.2174/2212796814999201111204639
Ankita Singh, V. Ranjan, R. Das, K. Bhatti, D. Mehta, Ram Mohan Chidurala
Innumerable reasons have been reported that affect and infect the liver and cause liver diseases. The evaluation and follow-up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, it has become evident that this once defined as “gold-standard” is now not the best method as it involves many limitations. Attempts to reveal non-invasive diagnostic tools have generated serum biomarkers, multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and are less expensive than a liver biopsy. Biomarkers have various advantages like minimally invasive, easy to apply with great availability and easier reproducibility, useful for monitoring therapy and less expensive. But then, direct biomarkers involved in extracellular matrix turnover need further validation in different geographic population and indirect biomarkers may not predict early pathophysiological changes in liver parenchyma. The accuracy and diagnostic value of most, if not all, of these biomarkers remain controversial. Hence, there is a need for a biomarker that is specific for the liver and can identify the magnitude of the clinical outcome of the disease. In this review, we discuss the clinical utility, limitations, and development of noninvasive biomarkers in their use as diagnostic and prognostic tests and analyze whether the present known serum biomarkers are laudable and accurate tools for the diagnosis of liver diseases.
{"title":"Serum Biomarkers for Noninvasive Diagnosis of Liver Diseases: How Laudable are These Tools?","authors":"Ankita Singh, V. Ranjan, R. Das, K. Bhatti, D. Mehta, Ram Mohan Chidurala","doi":"10.2174/2212796814999201111204639","DOIUrl":"https://doi.org/10.2174/2212796814999201111204639","url":null,"abstract":"\u0000\u0000Innumerable reasons have been reported that affect and infect the liver and cause liver\u0000diseases. The evaluation and follow-up of liver fibrosis and cirrhosis have been traditionally performed\u0000by liver biopsy. However, it has become evident that this once defined as “gold-standard”\u0000is now not the best method as it involves many limitations. Attempts to reveal non-invasive diagnostic\u0000tools have generated serum biomarkers, multiple scores, formulae, and imaging modalities.\u0000All are better tolerated, safer, more acceptable to the patient, and are less expensive than a liver\u0000biopsy. Biomarkers have various advantages like minimally invasive, easy to apply with great availability\u0000and easier reproducibility, useful for monitoring therapy and less expensive. But then, direct\u0000biomarkers involved in extracellular matrix turnover need further validation in different geographic\u0000population and indirect biomarkers may not predict early pathophysiological changes in liver\u0000parenchyma. The accuracy and diagnostic value of most, if not all, of these biomarkers remain controversial.\u0000Hence, there is a need for a biomarker that is specific for the liver and can identify the\u0000magnitude of the clinical outcome of the disease.\u0000\u0000\u0000\u0000In this review, we discuss the clinical utility, limitations, and development of noninvasive biomarkers\u0000in their use as diagnostic and prognostic tests and analyze whether the present known serum biomarkers\u0000are laudable and accurate tools for the diagnosis of liver diseases.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73014274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-11-02DOI: 10.2174/2212796814999201102195651
Iván R Vega-Valdez, Rosalez Melvin N., Santiago-Quintana José M., Farfán-García Eunice D., Soriano-Ursúa Marvin A.
Treatment of the COVID19 pandemic requires drug development. Boron- containing compounds are attractive chemical agents, some of them act as proteases inhibitors. The present study explores the role of boronic moieties in molecules interacting on the binding site of the SARS-CoV-2 main protease. Conventional docking procedure was applied by assaying boron-free and boron-containing compounds on the recently reported crystal structure of SARS-CoV-2 main protease (PDB code: 6LU7). The set of 150 ligands includes bortezomib and inhibitors of coronavirus proteases. Most of the tested compounds share contact with key residues and pose on the cleavage pocket. The compounds with a boron atom in their structure are often estimated to have higher affinity than boron-free analogues. Interactions and the affinity of boron-containing peptidomimetics strongly suggest that boron-moieties increase affinity on the main protease, which is tested by in vitro assays. A Bis-boron-containing compound previously tested active on SARS-virus protease and bortezomib were identified as potent ligands. These advances may be relevant to drug designing, in addition to testing available boron-containing drugs in patients with COVID19 infection.
{"title":"Docking Simulations Exhibit Bortezomib and other Boron-containing Peptidomimetics as Potential Inhibitors of SARS-CoV-2 Main Protease","authors":"Iván R Vega-Valdez, Rosalez Melvin N., Santiago-Quintana José M., Farfán-García Eunice D., Soriano-Ursúa Marvin A.","doi":"10.2174/2212796814999201102195651","DOIUrl":"https://doi.org/10.2174/2212796814999201102195651","url":null,"abstract":"\u0000\u0000 Treatment of the COVID19 pandemic requires drug development.\u0000Boron- containing compounds are attractive chemical agents, some\u0000of them act as proteases inhibitors.\u0000\u0000\u0000\u0000The present study explores the role of boronic moieties in molecules\u0000interacting on the binding site of the SARS-CoV-2 main protease.\u0000\u0000\u0000\u0000Conventional docking procedure was applied by assaying boron-free\u0000and boron-containing compounds on the recently reported crystal structure of\u0000SARS-CoV-2 main protease (PDB code: 6LU7). The set of 150 ligands includes\u0000bortezomib and inhibitors of coronavirus proteases.\u0000\u0000\u0000\u0000Most of the tested compounds share contact with key residues and pose\u0000on the cleavage pocket. The compounds with a boron atom in their structure are\u0000often estimated to have higher affinity than boron-free analogues.\u0000\u0000\u0000\u0000 Interactions and the affinity of boron-containing peptidomimetics\u0000strongly suggest that boron-moieties increase affinity on the main protease,\u0000which is tested by in vitro assays. A Bis-boron-containing compound previously\u0000tested active on SARS-virus protease and bortezomib were identified as potent ligands.\u0000These advances may be relevant to drug designing, in addition to testing\u0000available boron-containing drugs in patients with COVID19 infection.\u0000","PeriodicalId":10784,"journal":{"name":"Current Chemical Biology","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84600434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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