ABSTRACT
The upsurge of multiple drug resistance (MDR) bacteria substantially diminishes the effectiveness of antibiotic arsenal and therefore intensifies the rate of therapeutic failure. The major factor in MDR is efflux pump-mediated resistance. A unique pump can make bacteria withstand a wide range of struc-turally diverse compounds. Therefore, their inhibition is a promising route to eliminate resistance phenomenon in bacteria. Phytochemicals are excellent alternatives as resistance-modifying agents. They can directly kill bacteria or interact with the crucial events of pathogenicity, thereby decreasing the ability of bacteria to develop resistance. Numerous botanicals display noteworthy efflux pumps inhibi-tory activities. Edible plants are of growing interest. Likewise, some plant families would be excellent sources of efflux pump inhibitors (EPIs) including Apocynaceae, Berberidaceae, Convolvulaceae, Cucur-bitaceae, Fabaceae, Lamiaceae, and Zingiberaceae. Easily applicable methods for screening plant-derived EPIs include checkerboard synergy test, berberine uptake assay and ethidium bromide test. In silico high-throughput virtual detection can be evaluated as a criterion of excluding compounds with efflux substrate-like characteristics, thereby improving the selection process and extending the identification of EPIs. To ascertain the efflux activity inhibition, real-time PCR and quantitative mass spectrometry can be applied. This review emphasizes on efflux pumps and their roles in transmitting bacterial resistance and an update plant-derived EPIs and strategies for identification.
ABSTRACT
Background: Cancer constitutes a major hurdle worldwide and its treatment mainly relies onchemotherapy.Objectives: The present study was designed to evaluate the cytotoxicity of eleven naturally occurringcompounds including six phenolics amongst them were 4 chalcones and 2 flavanones as well as 5 terpenoids (3 clerodane and 2 trachylobane diterpenoids) against 6 human carcinoma cell lines and normalCRL2120 fibroblasts.Materials and methods: The neutral red uptake (NR) assay was used to evaluate the cytotoxicity of thecompounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle and mitochondrialmembrane potential (MMP) were all analyzed via flow cytometry meanwhile levels of reactive oxygenspecies (ROS) was measured by spectrophotometry.Results: Chalcones: 20,40-dihydroxy-60-methoxychalcone (1); 40,60-dihydroxy-20,50-dimethoxychalcone(2); 20,40,60-trihydroxy-50-methoxychalcone (3); 20,60-diacetate-40-methoxychalcone (4), trachylobanediterpenoids: 2,6,19-trachylobanetriol; (ent-2a,6a)-form (10) and 2,18,19-trachylobanetriol; (ent-2a)-form (11) as well as doxorubicin displayed IC50 values below 110 mM in the six tested cancer cell lines. TheIC50 values of the most active compounds were between 6.30 mM and 46.23 mM for compound 1respectively towards breast adenocarcinoma MCF-7 cells and small lung cancer A549 cells and between0.07 mM and 1.01 mM for doxorubicin respectively against SPC212 cells and A549 cells. Compounds 1induced apoptosis in MCF-7 cells mediated by increasing ROS production and MMP loss.Conclusion: Chalcones 1e3 are potential cytotoxic phytochemicals that deserve more investigations todevelop novel anticancer drugs against human carcinoma.© 2018 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Publishing Services byElsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).