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      Antitubercular evaluation of root extract and isolated phytochemicals from Lophira lanceolata against two resistant strains of Mycobacterium tuberculosis

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          Abstract

          Context: The roots of Lophira lanceolata Van Tiegh. Ex Keay (Ochnaceae) have numerous medicinal values in the Central African region. Even though the MeOH extract of the roots has shown antimycobacterial activities, the constituents responsible for this inhibitory activity remain unknown.

          Objective: Phytochemical investigation of the MeOH root extract of L. lanceolata and determination of the antimycobacterial activities of that extract and constituents against the growth of Mycobacterium tuberculosis.

          Materials and methods: Column chromatography was used to provide bioactive phytoconstituents. Those compounds were elucidated using MS and NMR spectroscopic data. Antimycobacterial screening of the extract (4.882–5000 µg/mL in DMSO during 24 h at 37 °C) and isolated compounds (0.244–250 µg/mL in DMSO during 24 h at 37 °C) was performed by microplate alamar blue assay (MABA) against two mycobacterial strains.

          Results: The investigation of L. lanceolata MeOH roots extract provided of mixture of unseparated biflavonoids with a newly described one, dihydrolophirone A ( 1a) associated to lophirone A ( 1b). The bioactive compounds that effectively inhibited the growth of M. tuberculosis AC45 were found to be compounds 1 and 2. They exhibited MIC values of 31.25 and 15.75 µg/mL, respectively, and their MIC was found to be 62.5 µg/mL against resistant strain AC83.

          Discussion and conclusions: It is clearly evident from the results obtained that the mycobacterial activity of L. lanceolata could be related mainly to its steroid and flavonoid contents. Therefore, this study suggests the potential of the above-mentioned classes of compounds as promising candidate agents for developing new anti-tuberculosis drugs.

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          Most cited references34

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          Antioxidant capacity of 26 spice extracts and characterization of their phenolic constituents.

          Total equivalent antioxidant capacity (TEAC) and phenolic content of 26 common spice extracts from 12 botanical families were investigated. Qualitative and quantitative analyses of major phenolics in the spice extracts were systematically conducted by reversed-phase high-performance liquid chromatography (RP-HPLC). Many spices contained high levels of phenolics and demonstrated high antioxidant capacity. Wide variation in TEAC values (0.55-168.7 mmol/100 g) and total phenolic content (0.04-14.38 g of gallic acid equivalent/100 g) was observed. A highly positive linear relationship (R2= 0.95) obtained between TEAC values and total phenolic content showed that phenolic compounds in the tested spices contributed significantly to their antioxidant capacity. Major types of phenolic constituents identified in the spice extracts were phenolic acids, phenolic diterpenes, flavonoids, and volatile oils (e.g., aromatic compounds). Rosmarinic acid was the dominant phenolic compound in the six spices of the family Labiatae. Phenolic volatile oils were the principal active ingredients in most spices. The spices and related families with the highest antioxidant capacity were screened, e.g., clove in the Myrtaceae, cinnamon in the Lauraceae, oregano in the Labiatae, etc., representing potential sources of potent natural antioxidants for commercial exploitation. This study provides direct comparative data on antioxidant capacity and total and individual phenolics contents of the 26 spice extracts.
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            Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium.

            In response to the need for rapid, inexpensive, high-throughput assays for antimycobacterial drug screening, a microplate-based assay which uses Alamar blue reagent for determination of growth was evaluated. MICs of 30 antimicrobial agents against Mycobacterium tuberculosis H37Rv, M. tuberculosis H37Ra, and Mycobacterium avium were determined in the microplate Alamar blue assay (MABA) with both visual and fluorometric readings and compared to MICs determined in the BACTEC 460 system. For all three mycobacterial strains, there was < or = 1 dilution difference between MABA and BACTEC median MICs in four replicate experiments for 25 to 27 of the 30 antimicrobics. Significant differences between MABA and BACTEC MICs were observed with 0, 2, and 5 of 30 antimicrobial agents against H37Rv, H37Ra, and M. avium, respectively. Overall, MICs determined either visually or fluorometrically in MABA were highly correlated with those determined in the BACTEC 460 system, and visual MABA and fluorometric MABA MICs were highly correlated. MICs of rifampin, rifabutin, minocycline, and clarithromycin were consistently lower for H37Ra compared to H37Rv in all assays but were similar for most other drugs. M. tuberculosis H37Ra may be a suitable surrogate for the more virulent H37Rv strain in primary screening of compounds for antituberculosis activity. MABA is sensitive, rapid, inexpensive, and nonradiometric and offers the potential for screening, with or without analytical instrumentation, large numbers of antimicrobial compounds against slow-growing mycobacteria.
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              Antimycobacterial plant terpenoids.

              Abstract. Tuberculosis (TB), mainly caused by Mycobacterium tuberculosis, is the leading killer among all infectious diseases worldwide and is responsible for more than two million deaths annually. For over thirty years no antitubercular agents with new mechanisms of action have been developed. The recent increase in the number of multi-drug resistant clinical isolates of M. tuberculosis has created an urgent need for the discovery and development of new antituberculosis leads. This review covers recent reports on plant-derived terpenoids that have demonstrated moderate to high activity in in vitro bioassays against M. tuberculosis. In this review, mono-, sesqui-, di- and triterpenes, and sterols, their structural analogs and semisynthetic derivatives will be discussed, with particular emphasis on the structural features essential for antimycobacterial activity.
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                Author and article information

                Journal
                Pharm Biol
                Pharm Biol
                IPHB
                iphb20
                Pharmaceutical Biology
                Taylor & Francis
                1388-0209
                1744-5116
                2018
                03 July 2018
                : 56
                : 1
                : 318-324
                Affiliations
                [a ]Department of Organic Chemistry, Faculty of Science, University of Yaoundé I , Yaoundé, Cameroon;
                [b ]Department Chemie, Universität Fribourg , Fribourg, Switzerland;
                [c ]Department of Chemistry, Higher Training College University of Yaoundé I , Yaoundé, Cameroon;
                [d ]Faculty of Chemistry, Philipps-Universität Marburg , Marburg, Germany;
                [e ]Department of Microbiology, Faculty of Science, University of Yaoundé I , Yaoundé, Cameroon
                Author notes
                CONTACT Dominique Serge Ngono Bikobo ngonosh@ 123456gmail.com Department of Organic Chemistry, Faculty of Science, University of Yaoundé I , P.O. Box 812, Yaoundé, Cameroon

                Supplemental data for this article can be accessed here .

                Article
                1476559
                10.1080/13880209.2018.1476559
                6130701
                29969355
                d7dd7219-f537-4677-9ba0-c95c10041b3f
                © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 December 2017
                : 31 March 2018
                : 09 May 2018
                Page count
                Pages: 7, Words: 6014
                Funding
                Funded by: Swiss National Science Foundation (SNSF) 10.13039/IZK0Z2-157272
                Award ID: IZK0Z2-
                Award ID: 72
                The authors gratefully acknowledge financial support from the Swiss National Science Foundation (SNSF) (No.: IZK0Z2-157272) for research fellowships in Switzerland to D. S. Ngono Bikobo. The authors also acknowledge the DAAD/STIBET Doktoranden Scholarship for financial support and travel grants for Mr. Mbabi to Germany.
                Categories
                Research Article

                ochnaceae,dihydrolophirone a,biflavonoids,steroids,antitubercular activity

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