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Fulltext In vitro cytotoxic and antimicrobial activities of Erythrina suberosa (Roxb) bark

Ahmed Z, Aziz S, Alauddin S, Mohiuddin SG, Javed A, Ahmed R, et al.

J Pharm Bioallied Sci, 2020 04 10;12(2):210-216.
PMID: 32742121 DOI: 10.4103/jpbs.JPBS_223_19

Background: The study was focused on evaluating cytotoxic and antimicrobial activities of Erythrina suberosa (Roxb.) bark through in vitro pharmacological screening.
Materials and Methods: The bark was extracted using different solvents, for example, dichloromethane, ethyl acetate, methanol, and aqueous for obtaining the organic fractions. These organic fractions were then evaluated for their cytotoxic and antimicrobial activity compared with the standard. Cefixime was used as the standard for antibacterial assay, whereas clotrimazole was used as the standard for antifungal activities. Bacterial strains used were Staphylococcus aureus and methicillin-resistant S. aureus (MRSA), whereas for antifungal activities Candida albicans, Candida parapsilosis, and Candida krusei strains were used.
Results: The organic fractions obtained were evaluated for their cytotoxic and antimicrobial activities. In cytotoxic assay (Brine shrimp lethality assay), dichloromethane fraction was the most potent with LD50 of 47.63, whereas aqueous, methanol, and ethyl acetate fractions showed LD50 of 121.74, 422.2, and 201.96, respectively. Similarly, for antibacterial assay, dichloromethane fraction showed 32.2mm zone of inhibition against MRSA in comparison with standard cefixime (zone of inhibition, 30.5mm). A minimal zone of inhibition with crude saponins (13.1 and 12.2mm) was observed against C. albicans in comparison to standard (cefixime) with a zone of inhibition of 28.5mm. No prominent results were observed against C. parapsilosis and C. krusei strains.
Conclusion: The study was based on the plant from Indo-Pak origin, and it has shown some prominent cytotoxic and antibacterial activities. Although the results of this study have provided a basic idea about the efficacy of plant extract, still more explanatory and high-scale studies can be beneficial for elaborating the cytotoxic and antimicrobial activities of this plant.

Matched MeSH terms: Clotrimazole
Fulltext In silico identification of novel tuberculosis drug targets in mycobacterium tuberculosis P450 enzymes by interaction study with azole drugs

Suresh Kumar

Malaysian Journal of Medicine and Health Sciences, 2020;16(101):24-30.
MyJurnal

Introduction: Tuberculosis (TB) is one of the utmost serious infectious diseases worldwide. The emergence of multi- drug resistance demands the development of better or new putative drug targets for tuberculosis. Recent studies sug- gest Mycobacterium tuberculosis cytochrome P450 enzymes as promising drug targets and azole drugs as potential inhibitors. Methods: Various computational tools, like Expasy Protparam, Swiss model, RaptorX and Phyre2 were used to analyze 12 Mycobacterium tuberculosis P450 enzymes and determine their three-dimensional structure. The structural validation was done through a Ramachandran plot using RAMPAGE server. The docking of P450 enzymes with azole drugs was done with autodock ver 4.2.6. Results: Based on sub-cellular localization prediction using CEL- LO tool, P450 enzymes CYP123A1, CYP132A1, CYP135A1, CYP136A1, CYP140A1, and CYP143A1 were predicted to be in the cytoplasm. Through structure assessment by Ramachandran plot, the best homology modelled proteins were docked with azole drugs like clotrimazole, croconazole, econazole, fluconazole, itraconazole, itraconazole, ketaconazole and micronazole by using autodock. By docking method it is identified that ketaconazole drug has a high affinity towards most of the mycobacterium P450 enzymes followed by the itrconazole drug. CYP123A1 enzyme is preferable as a drug target due to high binding affinity towards ketoconazole followed by CYP135A1, CYP140A1 enzymes. Conclusion: This study would help in identifying putative novel drug targets in Mycobacterium tuberculosis, which can lead to promising candidates for the optimization and development of novel anti-mycobac- terial agents.

Matched MeSH terms: Clotrimazole
Genetic diversity, antifungal susceptibility and enzymatic characterisation of Malaysian clinical isolates of Candida glabrata

Lotfalikhani A, Khosravi Y, Sabet NS, Na SL, Ng KP, Tay ST

Trop Biomed, 2018 Dec 01;35(4):1123-1130.
PMID: 33601859

Candida glabrata has been reported as the second or third most common yeast species isolated from patients with vaginitis and invasive candidiasis. This study was aimed to determine the genetic diversity, antifungal susceptibility and enzymatic profiles of C. glabrata isolated from vaginal and blood samples in the Medical Microbiology Diagnostic Laboratory, University Malaya Medical Centre. A random amplified polymorphic DNA (RAPD) analysis method, using M13 and (GTG)5 primers, was used for strain differentiation of C. glabrata isolates. Antifungal susceptibility testing of C. glabrata isolates was determined using E-test against amphotericin B, caspofungin, fluconazole and voriconazole and microbroth dilution method against clotrimazole. The enzymic profiles of C. glabrata were determined using APIZYM semi-quantitation kit and egg-yolk agar method. A total of 14 RAPD patterns were identified amongst C. glabrata isolates investigated this study. Susceptibility to amphotericin B, caspofungin, fluconazole and voriconazole was noted. Approximately one third of the isolates demonstrated resistance to clotrimazole (MIC>=1 µg/ml). A single isolate of C. glabrata was resistant to caspofungin (MIC:1.5 µg/ml). Enzymatic activities of acid and alkaline phosphatase, aminopeptidases, esterase and lipase and phospholipase were detected in the C. glabrata isolates. The genetic diversity and antifungal susceptibility profiles of C. glabrata isolates were presented in this study. Continued surveillance and monitoring of the incidence and antifungal resistance in C. glabrata isolates is necessary.

Matched MeSH terms: Clotrimazole
Green synthesis of selenium-N-heterocyclic carbene compounds: Evaluation of antimicrobial and anticancer potential

Kamal A, Nazari V M, Yaseen M, Iqbal MA, Ahamed MBK, Majid ASA, et al.

Bioorg Chem, 2019 09;90:103042.
PMID: 31226469 DOI: 10.1016/j.bioorg.2019.103042

Three benzimidazolium salts (III-V) and respective selenium adducts (VI-VIII) were designed, synthesized and characterized by various analytical techniques (FT-IR and NMR 1H, 13C). Selected salts and respective selenium N-Heterocyclic carbenes (selenium-NHC) adducts were tested in vitro against Cervical Cancer Cell line (Hela), Breast Adenocarcinoma cell line (MCF-7), Retinal Ganglion Cell line (RGC-5) and Mouse Melanoma Cell line (B16F10) using MTT assay and the results were compared with standard drug 5-Fluorouracil. Se-NHC compounds and azolium salts showed significant anticancer potential. Molecular docking studies of compounds (VI, VII and VIII) showed strong binding energies and ligand affinity toward following angiogenic factors: VEGF-A (vascular endothelial growth factor A), EGF (human epidermal growth factor), HIF (Hypoxia-inducible factor) and COX-1 (Cyclooxygenase-1) suggesting that the anticancer activity of adducts (VI, VII and VIII) may be due to their strong anti-angiogenic effect. In addition, compounds III-VIII were screened for their antibacterial and antifungal potential. Adduct VI was found to be potent anti-fungal agent against A. Niger with zone of inhibition (ZI) value 27.01 ± 0.251 mm which is better than standard drug Clotrimazole tested in parallel.

Matched MeSH terms: Clotrimazole
Increased expression and hotspot mutations of the multidrug efflux transporter, CDR1 in azole-resistant Candida albicans isolates from vaginitis patients

Looi CY, D' Silva EC, Seow HF, Rosli R, Ng KP, Chong PP

FEMS Microbiol Lett, 2005 Aug 15;249(2):283-9.
PMID: 16006060

The aims of our research were to investigate the gene expression of the multidrug efflux transporter, CDR1 and the major drug facilitator superfamily transporter, MDR1 gene in azole drug-resistant Candida albicans and Candida glabrata clinical isolates recovered from vaginitis patients; and to identify hotspot mutations that may be present in the C. albicans CaCDR1 gene that could be associated with drug-resistance. The relative expression of the CDR1 and MDR1 transcripts in ketoconazole and clotrimazole-resistant isolates and drug-susceptible ATCC strains were determined by semi-quantitative reverse transcription-polymerase chain reaction. Expression of CaCDR1 transcript was upregulated to varying extents in all three azole-resistant C. albicans isolates studied (1.6-, 3.7- and 3.9-fold) and all three C. glabrata isolates tested (at 1.9-, 2.3- and 2.7-fold). The overexpression level of CaCDR1 in the isolates correlated with the degree of resistance as reflected by the minimum inhibitory concentration (MIC) of the drugs. The messenger RNA for another efflux pump, MDR1, was also overexpressed in one of the azole-resistant C. albicans isolates that overexpressed CDR1. This finding suggests that drug-resistance may involve synergy between energy-dependent drug efflux pumps CDR1p and MDR1p in some but not all isolates. Interestingly, DNA sequence analysis of the promoter region of the CaCDR1 gene revealed several point mutations in the resistant clinical isolates compared to the susceptible isolates at 39, 49 and 151 nucleotides upstream from the ATG start codon. This finding provides new information on point mutations in the promoter region which may be responsible for the overexpression of CDR1 in drug-resistant isolates.

Matched MeSH terms: Clotrimazole/therapeutic use