Publications by authors named "Mansour Alturki"

4 Publications

  • Page 1 of 1

Enhanced Bioavailability of Boswellic Acid by : A Computational and Pharmacokinetic Study.

Front Pharmacol 2020 15;11:551911. Epub 2020 Dec 15.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, United States.

Chronic inflammation is a key culprit factor in the onset and progression of several diseases. Novel and pharmacologically effective therapeutic approaches are needed for new treatment remedy or improved pharmacokinetics and pharmacodynamics for existing synthetic drugs, in particular natural products. Boswellic acids are well-known natural products, with capacity to effectively retard inflammation without severe adverse effects. However, the therapeutic use of Boswellic acids are greatly hindered by its poor pharmacokinetic properties. Co-administration strategies that facilitate the oral absorption and distribution of Boswellic acids should lead to a safe and more effective use of this product prophylactically and therapeutically in inflammatory disorders. In this study, we examined the effect of extract on the absorption and bioavailability of Boswellic acid in rabbits. In addition, we further explored computational pharmacodynamic interactions between and Boswellic acid. extract at 2.5 and 10 mg/kg, increased the bioavailability of Boswellic acid ( < 0.05). Based on our drug-based computational modeling, cytochrome P450 (CYP450)-mediated mechanism was involved in increased bioavailability. These findings confirmed that with Boswellic acid may be administered orally together for effective therapeutic efficacy. Thus, our studies support the application of with Boswellic acid as a novel therapeutic avenue in diseases associated with inflammation.
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http://dx.doi.org/10.3389/fphar.2020.551911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770183PMC
December 2020

Slow-Binding Inhibition of Mycobacterium tuberculosis Shikimate Kinase by Manzamine Alkaloids.

Biochemistry 2018 08 31;57(32):4923-4933. Epub 2018 Jul 31.

Department of Drug Discovery and Development, Harrison School of Pharmacy , Auburn University , 4306 Walker Building , Auburn , Alabama 36849 , United States.

Tuberculosis represents a significant public health crisis. There is an urgent need for novel molecular scaffolds against this pathogen. We screened a small library of marine-derived compounds against shikimate kinase from Mycobacterium tuberculosis ( MtSK), a promising target for antitubercular drug development. Six manzamines previously shown to be active against M. tuberculosis were characterized as MtSK inhibitors: manzamine A (1), 8-hydroxymanzamine A (2), manzamine E (3), manzamine F (4), 6-deoxymanzamine X (5), and 6-cyclohexamidomanzamine A (6). All six showed mixed noncompetitive inhibition of MtSK. The lowest K values were obtained for 6 across all MtSK-substrate complexes. Time-dependent analyses revealed two-step, slow-binding inhibition. The behavior of 1 was typical; initial formation of an enzyme-inhibitor complex (EI) obeyed an apparent K of ∼30 μM with forward ( k) and reverse ( k) rate constants for isomerization to an EI* complex of 0.18 and 0.08 min, respectively. In contrast, 6 showed a lower K for the initial encounter complex (∼1.5 μM), substantially faster isomerization to EI* ( k = 0.91 min), and slower back conversion of EI* to EI ( k = 0.04 min). Thus, the overall inhibition constants, K*, for 1 and 6 were 10 and 0.06 μM, respectively. These findings were consistent with docking predictions of a favorable binding mode and a second, less tightly bound pose for 6 at MtSK. Our results suggest that manzamines, in particular 6, constitute a new scaffold from which drug candidates with novel mechanisms of action could be designed for the treatment of tuberculosis by targeting MtSK.
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http://dx.doi.org/10.1021/acs.biochem.8b00231DOI Listing
August 2018

A multifaceted approach to identify non-specific enzyme inhibition: Application to Mycobacterium tuberculosis shikimate kinase.

Bioorg Med Chem Lett 2018 02 5;28(4):802-808. Epub 2017 Dec 5.

Department of Drug Discovery and Development, Harrison School of Pharmacy, 4306 Walker Building, Auburn University, Auburn, AL 36849, USA. Electronic address:

Single dose high-throughput screening (HTS) followed by dose-response evaluations is a common strategy for the identification of initial hits for further development. Early identification and exclusion of false positives is a cost-saving and essential step in early drug discovery. One of the mechanisms of false positive compounds is the formation of aggregates in assays. This study evaluates the mechanism(s) of inhibition of a set of 14 compounds identified previously as actives in Mycobacterium tuberculosis (Mt) cell culture screening and in vitro actives in Mt shikimate kinase (MtSK) assay. Aggregation of hit compounds was characterized using multiple experimental methods, LC-MS, HNMR, dynamic light scattering (DLS), transmission electron microscopy (TEM), and visual inspection after centrifugation for orthogonal confirmation. Our results suggest that the investigated compounds containing oxadiazole-amide and aminobenzothiazole moieties are false positive hits and non-specific inhibitors of MtSK through aggregate formation.
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http://dx.doi.org/10.1016/j.bmcl.2017.12.002DOI Listing
February 2018

A study investigating the level of satisfaction with the health services provided by the Pharmacist at ENT hospital, Eastern Region Alahsah, Kingdom of Saudi Arabia.

Saudi Pharm J 2013 Jul 21;21(3):255-60. Epub 2012 Sep 21.

Clinical Pharmacist, Aljaber ENT hospital, Eastern Region Alahsa, Saudi Arabia.

The current study aims to evaluate the patient's level of satisfaction with health care services provided by the pharmacist at Aljaber ENT hospital, Eastern Region Alahsah, Kingdom of Saudi Arabia. A cross sectional study was planned from 1st March 2011 until 31st May 2011. A 27 item questionnaire was used, scoring of the responses was done to classify the patient satisfaction into sublevels. The maximum possible score was 36; those scoring less than twenty were graded as poor satisfaction level followed by moderate satisfaction level 21-25, good satisfaction level 26-30 and high satisfaction level 31-36. Statistical package for social science version 13® was used to analyze data, One-way ANOVA and independent sample t-test were applied to see the differences in the level of satisfaction. Every third patient visiting pharmacy was given a chance to participate in this study. A total of N = 991 patients were randomized using the pharmacy appointment number. Of whom 657 patients have shown willingness to participate in this study. The response rate of this study was 66.30%, most of the respondents 383 (58.1%) were male ranging from the age group of 21-40 years with a mean age of 32 years SD 9.73. The mean score for all patients was 26.15 SD ±3.4. Among all the demographic variables a significant difference in satisfaction level was found among in terms of age (df = 8, F = 8.36, p = <0.001(∗)), gender (t = -4.089, df = 656, p=<0.001(∗)) and race (df = 2, F = 8.47, p = <0.001. The satisfaction level among Saudi nationals was least in comparison to Egyptians and others. In general, it is seen that respondents of age 56-60 years were most satisfied with the healthcare services provided by the pharmacist. In addition, the satisfaction level was higher among female patients in comparison to men.
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http://dx.doi.org/10.1016/j.jsps.2012.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744925PMC
July 2013
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