Publications

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    Mahmoud E Balbaa, Reem Waheb, Riham Hosna
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    ABSTRACT: Aims: It is to screen many natural product extracts for their in vitro and in vivo effects on the activities of hepatic α-amylase and α-glucosidase to validate their biological importance. Study Design: Different groups of non-diabetic and diabetic rats were treated by different plants for the in vivo study of glycosidases. In vitro effect of the plants on the tested enzymes was studied in presence and absence of their aqueous extract. Place and Duration of Study: Department of Biological & Environmental Sciences, Faculty of Science, Beirut Arab University, Beirut, Lebanon, between March 2013 and February 2014. Methodology: Enzymes were extracted from the livers of normal rats, also the natural products extracts were prepared for the in vitro studies. α-Amylase and α-glucosidase assays were done in the presence and absence of each plant extract. For the in vivo studies, normal non-diabetic rats were divided into groups, whereas the first group is a control that includes rats fed on normal food diet. The other groups include rats fed on normal food diet mixed with the tested plant leaves (20 mg/g body weight/day) Diabetes was induced in diabetic rats by single intraperitonial injection of streptozotocin. Diabetic rats were divided into groups and treated like the non-diabetic rats. Results: Only Thymus vulgaris and Origanum vulgare extracts showed a significant in vitro dosedependent inhibition on α-amylase with IC50 values of 0.2±0.01 and 0.37±0.03mg/ml, respectively. However, the in vivo effect was not detected for four weeks treatment for the two enzymes. The in vitro treatment of α-amylase by Thymus vulgaris and Origanum vulgare extracts exhibited a mixedtype inhibition. Moreover, the in vivo inhibition of both extracts on the tested hepatic enzymes was not detected in streptozotocin-induced diabetic rats fed on Thymus vulgaris and Origanum vulgare for four weeks. Blood sugar level was non-significantly decreased with respect to that of nontreated rats. Conclusion: some non anti-diabetic plant extracts possess an in vitro inhibition of glycosidases.
    International Journal of Biochemistry Research & Review. 10/2015; 5(2):95-106.
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    ABSTRACT: The inhibition of glycosidases from bacteria and the liver of normal and diabetic rats by 2-(tetra-O-acetyl-β-Dglucopyranosylsulfanyl)- 5-(1-benzyl-1H-indol-2-yl)-1,3,4-oxadiazole BnM-3B; 3-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)- 5-(1H-indol-2-yl)-1,3,4-oxadiazole- 2(3H)-thione MTB-4A; 3-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-Dglucopyranosyl)- 5-(1-benzyl-1H-indol-2-yl)-1,3,4-oxadiazole-2(3H)-thione BnN-5A has been investigated. In vitro treatment of hepatic α-amylase and β-glucuronidase from control and streptozotocin-induced diabetic rats by S- and Nglycosyl analogues from oxadiazolinethione derivatives exhibited a significant dose-dependent decrease on the specific activity of both α-amylase and β-glucuronidase. Moreover, these compounds also exhibited a significant decrease on the specific activity of α-amylase and α-glucosidase produced by Bacillus subtilis AH. The observed IC50 values of these compounds are much lower than that of ethanolamines, higher for α-glucosidase than α-amylase from bacteria and significantly lower for hepatic α-amylase and β-glucuronidase from diabetic rats. The obtained results suggest that these compounds are good inhibitors that act on glycosidases from bacteria and normal / diabetic rats in different mechanisms.
    Letters in Drug Design &amp Discovery 01/2015; 12(3). · 0.85 Impact Factor
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    Rima Samarji, Mahmoud Balbaa
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    ABSTRACT: Background: Diabetes mellitus (DM) is characterized by the overproduction of the reactive oxygen species which affects the integrity of the lysosomal membrane affecting lysosomal enzymes. The effect of these species is blocked by some natural products as antioxidants. In the current study, groups of normal and streptozotocin (STZ)-induced diabetic rats were treated by Nigella sativa (NS), olive and canola oils and subjected to the study of arylsulfatases as a model of lysosomal enzymes. The aim of the present study is to investigate the effect of STZ-induced diabetes on arylsulfatases in presence and absence of NS, olive and canola oils. Methods: Different groups of rats were induced by STZ, treated with different oils and compared to their corresponding control group. All groups were subjected for the assays of blood glucose, insulin, catalase and arylsulfatases. A comparative kinetic study of arylsulfatses was performed to detect the alteration of catalytic characterization. Results: The results demonstrated that diabetes causes a significant elevation in the level of hepatic arylsulfatase B and a significant reduction of hepatic catalase as an antioxidant enzyme. NS and olive oils returned catalase and arylsulfatase B activities back near to normal by fixing their catalytic properties. Furthermore, the maximum velocity of arylsulfatases A and B was significantly elevated in the induced diabetes, whereas their Km values were significantly changed. The treatment of diabetic rats by NS and olive oils reduced the degree of significance. Conclusion: Diabetes induces significant alterations of the catalytic characters of arylsulfatases and some oils decrease this alteration through an antioxidant-mediated effect.
    Journal of Diabetes and Metabolic Disorders. 12/2014; 13(1).
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    ABSTRACT: This study included 20 selected female patients with breast cancer, 30 of their female relatives (sisters and daughters), and 10 healthy females as a control group. Genomic DNA was extracted from peripheral blood lymphocytes of all the subjects, and the polymerase chain reaction was carried out using specific primers for BRCA1 (exons 2 and 8) and BRCA2 (exons 9, 11, and 21). The mutations were detected using a single-strand conformation polymorphism assay and heteroduplex analysis. Finally, the sample variants and their controls were sequenced. Mutations were detected in 44% of the study population, with 18% found in the BRCA1 gene and 26% attributed to BRCA2. Five sequence variants were identified, including two frameshift mutations, one nonsense mutation, and two missense mutations. Therefore, we conclude that germline mutations in two major genes, BRCA1 and BRCA2, may have an important influence on the predisposition and development of familial breast cancer.
    Biochemical Genetics 02/2014; 52(1-2):15-28. · 0.94 Impact Factor
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    ABSTRACT: In this article, we present a study on the levels of epidermal growth factor (EGF), its phosphorylated receptor (p-EGFR) and transforming growth factor-β1 (TGF-β1) in the sera of patients with hepatocellular carcinoma (HCC) and chronic hepatitis C (CHC) infection. The results reveal significant higher serum levels of EGF and TGF-β1 in patients with HCC compared to their level in patients with CHC infection and control subjects. The levels of p-EGFR in HCC and CHC patients show a highly significant difference between patients. Based on the best cutoff value of 914 pg/ml, EGF shows 63.3 % sensitivity and 87.5 % specificity for HCC patients where the area under the curve is 0.81. The p-EGFR shows sensitivity of 63.3 % and specificity of 100 % where the area under the curve is 0.87 for HCC patients based on the best cutoff value of 39 U/mg protein. The best cutoff value (370 pg/ml) for serum TGF-β1 displays sensitivity of 86.7 % and specificity of 100 %, where the area under the curve is 0.97 for HCC patients.
    Medical Oncology 09/2013; 30(3):673. · 2.14 Impact Factor
  • Mahmoud E Balbaa
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    ABSTRACT: Background: Several drugs have been implicated as having various respiratory and cardiac effects. For example, phenobarbitone is a central nervous system sedative and is also an anticonvulsant. Neostigmine, which is a stimulant of the parasympathetic nervous system, acts as a reversible anti-cholinesterase for the treatment myasthenia gravis and certain types of glaucoma. Aminophylline is a vasodilator, which improves the cardiac index and pulmonary vascular resistance. Gallamine is considered as a muscle relaxant that has a cardiovascular effect [1]. On the other hand, the main respiratory chain in mitochondria consists of dehydrogenases, including succinate-cytochrome c reductase (SCR), linked to flavoproteins and the cytochrome system. This enzyme catalyzes the oxidation of succinate by cytochrome c (cyt c) or 2,6-dichlorophenolindophenol (DCIP) under optimal conditions. The reduction of DCIP by succinate was found to be highly dependent upon DCIP concentration [2]. Aims: In clinical applications, different types of enzymes were investigated in an attempt to reflect changes occurring in the different tissues. SCR was subjected for the current study to reveal the effect of the above mentioned drugs on the biological oxidation because of their clinical application without enough knowledge of their specific action on the enzymes of the respiratory chain. Methods: The mice were treated with different doses of the above mentioned drugs in saline by i.m. or s.e. injections. At the end of each infection period, the infected group and the corresponding control one were sacrificed. The livers were immediately removed, homogenized and centrifuged. The obtained supernatant was subjected to enzyme assay and the corresponding enzyme purification of the kinetic study. Results: SCR was inhibited in vitro and in vivo by phenobarbitone, aminopbylline and neostigmine using both DCIP and cyt c as substrates. The enzyme was also activated by gallamine towards both substrates. In vitro, phenobarbitone and aminophylline inhibited the enzyme with respect to the reduction of DCIP and cyt c in a non-competitive manner with Kj values of 1.5 X 10-5 and 5.7 x 10-5 M, respectively. Moreover, neostigmine competitively inhibited the enzyme towards both substrates with Kj values of 1.36 x 10-5 and 1.50 x 10-5 M, respectively. Conclusions: completely different mechanisms are operative through the effect of these drugs on the enzyme. References: [1] Balbaa, M., Al-Meer, J. and Al-Khal, A. (2004): Effect of some cardiac and respiratory drugs on succinate-cytochrome c reductase. J. Enzym. Inhib. Med. Chem., 19: 343. [2] Takemori, S. and King, T.E. {1964) J. Biol. Chem. 239, 3456.
    The 4th Chongqing International Clinical Neuroscience Forum & NeuroDrug, Chongqing, China; 11/2012
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    ABSTRACT: Coccidiosis is one of the most common parasitic diseases affecting many species of domestic animals. This disease has a major economic significance and the search for new compounds having anticoccidial activity is of great importance. In this article, different levels of protection from coccidian infection by Eimeria stiedae were developed in rabbits by treatment with compounds incorporating the skeleton of thiourea. These compounds include 4,5-diphenylimidazole-2-thione (1), 4,5-Diphenyl-1,2,4-triazole-3-thiol (2) and 5-(2-Hydroxyphenyl)-4-phenyl-1,2,4-triazole-3-thiol (3) compared to the anticoccidial drug toltrazuril as a reference compound. Compounds 1-3 inhibit coccidiosis-induced activity of α-glucosidase. The protection from coccidial infection by compound 1 was higher than that shown for compounds 2 and 3. These data suggest that diazole and triazole thione derivatives have a mimetic effect for anticoccidial drugs through their inhibition of glycosidases.
    Acta biochimica Polonica 10/2012; · 1.19 Impact Factor
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    MAHMOUD BALBAA and EL SAYED H. EL ASHRY
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    ABSTRACT: The enzyme inhibition is valuable in the regulation of the enzyme activity. It has many applications, which include the drug design to target an enzyme. In the present review, we focus on the inhibition of different enzymes such as glycosidases, arylsulfatases and others by synthetic inhibitors or drugs. This provides the strategy that combines the inhibitory and therapeutic mode of action of the confirmed inhibitors.
    Biochemistry & Physiology: Open Access. 01/2012; 1(2).
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    Natalia El-Merhie, Ismail Sabry, Mahmoud Balbaa
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    ABSTRACT: Calcium is an essential nutrient required for critical biological functions. Calcium supplementation is to be evaluated using immature female rats. The present study focused on some blood parameters, gonadal development and bone structure. Forty immature female Sprague-Dawley rats were randomly divided into four equal-sized groups (80 g average body weight) to receive calcium chloride dihydrate (group I: control; groups II, III and IV: received 20 mg, 40 mg and 60 mg per kg body weight, respectively) for 5 weeks. Rats were decapitated, and their trunk blood was sampled for biochemical assays. Cholesterol, triglycerides, glucose and calcium were measured. Gonadal and bone structure were histologically evaluated. Results revealed that treatment of developing female rats with three calcium doses used have no marked effect on the serum calcium and cholesterol levels. However, serum triglyceride level and body weight gain are significantly decreased in rats treated with all of the three calcium doses. Serum glucose level showed a marked increase in animals treated with the higher calcium doses. Moreover, observable histological alterations are recognized in the ovaries. Bones of the experimental animals also showed morphological alterations. These results suggest that increasing calcium supplementation decreases triglycerides and percentage body weight gain and positively affects the bone and gonadal development.
    Journal of physiology and biochemistry 12/2011; 68(2):219-27. · 1.65 Impact Factor
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    ABSTRACT: Mutations in the genes encoding enzymes involved in the metabolism of chemical carcinogens can significantly affect the risk of cell transformation and cancer development. The resident Lebanese population has experienced a sharp increase in cancer incidence within the last few years. The relationship between gene polymorphisms of metabolic enzymes and gastrointestinal (GI) cancer incidence was not previously investigated. The aim of this study was to investigate the relationship between CYP1A1, CYP2E1, and GSTM1 gene polymorphisms and GI cancer incidence among Lebanese. Blood and/or paraffin-embedded biopsy samples were collected from patients and healthy controls. The genotypes were determined by polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism. The results of the present case-control study show that the studied Lebanese population generally resembles Caucasian populations with respect to the considered polymorphisms. Further, the GSTM1*0/*0 genotype is a significant risk factor for gastric (odds ratio = 4.1; 95% confidence interval: 1.2-14.5) and colorectal cancers (odds ratio = 3.8; 95% confidence interval: 1.7-8.5); on the other hand, CYP1A1*2A and CYP2E1*6 alone are not significantly associated with GI cancer development, although CYP1A1*2A was more frequent among patients. A remarkable and statistically significant 36.5-fold increase in the risk of gastric cancer was observed among patients with CYP1A1*2A/*2A combined with GSTM1*0/*0. The investigation of genetic risk factors and susceptibility gene polymorphisms in Lebanese is helpful for better understanding of GI cancer etiology.
    Genetic Testing and Molecular Biomarkers 06/2011; 15(6):423-9. · 1.44 Impact Factor
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    ABSTRACT: The in vivo and in vitro effects of 4,5-diphenylimidazole-2-thione (1), 4,5-diphenyl-1,2,4-triazole-3-thiol (2) and 5-(2-hydroxyphenyl)-4-phenyl-1,2,4-triazole-3-thiol (3) on α-glucosidase and α-amylase were investigated. The in vivo inhibition has been found to be dose-dependent and to occur at a value less than LD50. The in vitro treatment of the enzymes by 4,5-diphenylimidazole-2-thione exhibited a reversible inhibition of the non-competitive type with Ki value of 3.5 and 6.5×10(-5) M for α-glucosidase and α-amylase, respectively. 4,5-diphenyl-1,2,4-triazole-3-thione showed a reversible inhibition of the competitive and non-competitive types, with Ki value of 10(-5) M magnitude, for α-glucosidase and α-amylase. On the other hand, 5-(o-hydroxyphenyl)-4-phenyl-1,2,4-triazole-3-thione did not display an inhibitory effect towards α-amylase but showed a potent inhibition of the competitive type for hepatic α-glucosidase with 10(-5) M magnitude of Ki value.
    European Journal of Medicinal Chemistry 06/2011; 46(6):2596-601. · 3.43 Impact Factor
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    ABSTRACT: Mutations in the genes encoding enzymes involved in the metabolism of chemical carcinogens can significantly affect the risk of cell transformation and cancer development. The resident Lebanese population has experienced a sharp increase in cancer incidence within the last few years. The relationship between gene polymorphisms of metabolic enzymes and gastrointestinal (GI) cancer incidence was not previously investigated. The aim of this study was to investigate the relationship between CYP1A1, CYP2E1, and GSTM1 gene polymorphisms and GI cancer incidence among Lebanese. Blood and/or paraffin-embedded biopsy samples were collected from patients and healthy controls. The genotypes were determined by polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism. The results of the present case-control study show that the studied Lebanese population generally resembles Caucasian populations with respect to the considered polymorphisms. Further, the GSTM1*0/*0 genotype is a significant risk factor for gastric (odds ratio = 4.1; 95% confidence interval: 1.2-14.5) and colorectal cancers (odds ratio = 3.8; 95% confidence interval: 1.7-8.5); on the other hand, CYP1A1*2A and CYP2E1*6 alone are not significantly associated with GI cancer development, although CYP1A1*2A was more frequent among patients. A remarkable and statistically significant 36.5-fold increase in the risk of gastric cancer was observed among patients with CYP1A1*2A/*2A combined with GSTM1*0/*0. The investigation of genetic risk factors and susceptibility gene polymorphisms in Lebanese is helpful for better understanding of GI cancer etiology.
    Genetic Testing and Molecular Biomarkers 03/2011; 15(6):423-9. · 1.44 Impact Factor
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    ABSTRACT: Enzymes in mitochondria play an important role in biological oxidation and energy production. To understand the effect of schistosomiasis on these important processes, succinate cytochrome c reductase (SCR) from control and Schistosoma-infected mice was subjected for investigation. In this article, we report that SCR from Schistosoma-infected mouse showed a significant decrease in its Vmax and Km compared to control using both cytochrome c and 2,6-dichlorophenolindophenol as substrates. Furthermore, the kinetic studies of the purified SCR in the absence and presence of the schistosomicidal drugs praziquantel and Commiphora extract reveal that both drugs have an inhibitory action on the enzyme from the control and Schistosoma-infected mice and praziquantel changes the type of inhibition of SCR towards cytochrome c from mixed type in control to a competitive one in the case of the infection.
    Journal of physiology and biochemistry 12/2010; 66(4):291-9. · 1.65 Impact Factor
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    ABSTRACT: Quinazolinone derivatives have been studied as both in vitro and in vivo inhibitors of aspartate transcarbamylase (ATCase). In vitro treatment of mammalian ATCase with four compounds revealed that they inhibited enzyme activity and that 2-phenyl-1,3-4(H)benzothiazin-4-thione was the most potent one. This compound acts as a noncompetitive inhibitor towards both aspartate and carbamoyl phosphate. The values of the inhibition constant (K(i)) indicate that this compound exerts a potent inhibitory effect upon ATCase activity. Moreover, in vivo treatment with different doses of these derivatives showed also an inhibitory effect upon ATCase, the relative activity being decreased by 40%-58% with a 1 mg dose. These data support the inhibition of ATCase by quinazolinone derivatives as a new type of inhibitor for the enzyme.
    Journal of Enzyme Inhibition and Medicinal Chemistry 09/2008; 23(4):483-92. · 1.50 Impact Factor
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    ABSTRACT: Quinazolinone derivatives are structurally related to pyrimidines, which possess a wide range of biological properties [1-3]. These compounds are subjected to both in vitro and in vivo studies of aspartate transcarbamylase (ATCase). In vitro treatment of ATCase with four compounds revealed that they inhibited the enzyme activity and 2- phenyl-1,3-4(H)benzothiazin-4-thione is the most potent one. This compound acts as a noncompetitive inhibitor toward both aspartate and carbamoyl phosphate. The values of inhibition constant (Ki) indicate that this compound has a potent inhibitory effect upon ATCase activity. Moreover, in vivo treatment with different doses of these derivatives showed also an inhibitory effect upon ATCase, whereas the relative activity was decreased by 40% - 58% with one mg dose. These data support that the inhibition of ATCase by quinazolinone derivatives may be attributed to an impaired regulation of the enzyme as a result of a reversible binding to these compounds. References: A. Kumar, S. Sharma, Archana, K. Bajaja, S. Sharma, H. Panwar, T. Singh, V. K. Srivastava. Bioorg. Med. Chem., 11: 5293 (2003). J. W. Perrine, W. J. Houlihan, E. I. Takesue. Arzneim.-Forsch., 34: 879 (1984). H. Chen, W. Chen, L. Gan, A. E. Mutlib. Drug Metab. Dispos., 31: 122 (2003).
    2nd European Conference on Chemistry for Life Sciences, Wroclaw, Poland; 09/2007
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    Mahmoud Balbaa, Khaled Bassiouny
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    ABSTRACT: Arylsulfatase B (ASB) hydrolyzes the desulfation of N-acetylgalactosamine-4-sulfate at the non-reducing terminal of glycosaminoglycans. This enzyme activity was found to be elevated in mice schistosomiasis. In the present study, the catalytic and immunological properties of purified ASB from the liver of Schistosoma-infected mouse was investigated in the presence and absence of the schistosomicidal drugs praziquantel and Commiphora extract. The in vitro effect of praziquantel was found to be inhibitory with a Ki value of 5.5 x 10(-4) M while that of commiphora extract was as an activator. Furthermore, these drugs did not have an observed effect on the immunological properties of ASB with regard to its binding to its polyclonal rabbit antibody. These results indicate that some schistosomicidal drugs may reverse the alteration of the catalytic properties of the enzyme in schistosomiasis.
    Journal of Enzyme Inhibition and Medicinal Chemistry 03/2006; 21(1):81-5. · 1.50 Impact Factor
  • Mahmoud Balbaa, Jehan Al-Meer, Amina Al-Khal
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    ABSTRACT: Succinate-cytochrome c reductase was inhibited in vitro and in vivo by phenobarbitone, aminophylline and neostigmine using both 2,6-dichlorophenolindophenol (DCIP) and cytochrome c (cyt c) as substrates. The enzyme was also activated by gallamine towards both substrates. In vitro, phenobarbitone and aminophylline inhibited the enzyme with respect to the reduction of DCIP and cyt c in a non-competitive manner with Ki values of 1.5 x 10(-5) and 5.7 x 10(-5)M, respectively. Moreover, neostigmine competitively inhibited the enzyme towards both substrates with Ki values of 1.36 x 10(-5) and 1.50 x 10(-5)M, respectively.
    Journal of Enzyme Inhibition and Medicinal Chemistry 09/2004; 19(4):343-7. · 1.50 Impact Factor
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    ABSTRACT: The levels of arylsulfatases A and B, alpha-amylase, aspartate transcarbamylase, and gamma-glutamyl transpeptidase were investigated during the infection of mice with schistosoma mansoni. This infection caused a significant (p < 0.001) increase in the activity of hepatic arylsulfatase B (ASB), aspartate transcarbamylases and gamma-glutamyl transpeptidase. A non-significant difference occurred for alpha-amylase (p < 0.3) and arylsulfatase A (p > 0.5) when compared to the control. The specific activity of hepatic ASB was progressively increased with the progression of the Schistosoma-infection. Moreover, the kinetic studies of hepatic ASB in Schistosoma-infection showed that a slight decrease in the value of K(m) and about a 40% increase in V(max) when compared to the control. In addition, the pH optimum of hepatic ASB was altered from 6 to 7 as a result of schistosomiasis. These observations suggest that there are schistosomiasis-associated changes of the catalytic and kinetic properties of hepatic ASB.
    Journal of biochemistry and molecular biology 03/2004; 37(2):223-8. · 2.02 Impact Factor
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    ABSTRACT: The in vivo and in vitro effects of 4-amino-3-(D-glucopentitol-1-yl)-5-mercapto-1,2,4-triazole and its 3-methyl analogue on alpha- and beta-glucosidases, beta-glucuronidase as well as alpha-amylase have been investigated. alpha-Glucosidase is the enzyme that is markedly affected in vivo and in vitro in a dose-dependent manner. The compounds showed a reversible inhibition of a competitive type for alpha-glucosidase. Moreover, they exert a relatively potent inhibition on alpha-glucosidase with a Ki magnitude of 3.6 x 10(-4), 9.5 x 10(-5) M.
    Nucleosides Nucleotides &amp Nucleic Acids 11/2002; 21(10):695-708. · 0.71 Impact Factor
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    ABSTRACT: The in vivo and in vitro effects of 4-amino-3-(D-glucopentitol-l-yl)-5-mercapto-1,2,4-triazole and its 3-methyl analogue on α- and β-glucosidases, β-glucuronidase as well as α-amylase have been investigated. α-Glucosidase is the enzyme that is markedly affected in vivo and in vitro in a dose-dependent manner. The compounds showed a reversible inhibition of a competitive type for α-glucosidase. Moreover, they exert a relatively potent inhibition on α-glucosidase with a Ki magnitude of 3.6×10, 9.5×10 M.
    Nucleosides Nucleotides &amp Nucleic Acids 01/2002; 21(10):695-708. · 0.71 Impact Factor

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