study, we performed pharmacodynamics (PD) evaluation. The results show that the PD of RMP was subtherapeutic. Together, these observations emphasize the need for optimizing the drug dosage based on the PD of large-scale studies conducted in different geographical settings.
Mannich bases and its derivatives are regarded as supreme pharmacophores in therapeutics. The study investigates the antimycotic potential of Mannich bases, 1-((1H-benzimidazol-1-yl) methyl) urea (C1) and 1-((3-hydroxynapthalen-2-yl) methyl) thiourea (C2), against Candida albicans. Biofilm and hyphal inhibitory activities of the Mannich bases were tested by crystal violet quantification, fluorescence imaging cAMP rescue, qRT PCR, and by molecular docking analysis. The compounds inhibited the biofilms of C. albicans and restrained the filamentation abilities of the pathogen. Structure-activity relationship studies revealed that the presence of urea or thiourea moiety in the tail section is essential for interacting with adenylate cyclase (AC). The Mannich bases seemed to block Ras-cAMP-PKA pathway by inhibiting second messenger activity required for hyphal induction and biofilm formation. In conclusion, the study warrants point-of-care testing of C1/C2 and provides a starting point for deriving several structurally modified Mannich bases which might plausibly replace the prevailing antimycotic drugs in future.
Development of molecular markers for specific detection of microbial pathogens using real-time polymerase chain reaction (PCR) is an appealing and challenging technique. A real-time PCR is an emerging technology frequently used to detect the aetiologic agents. In recent times, designing species-specific primers for pathogen detection is gaining momentum. The method offers rapid, accurate and cost-effective strategy to identify the target, thus providing sufficient time to instigate appropriate chemotherapy. The study highlights the use of intein DNA sequence as molecular markers for species-specific identification of Candida tropicalis. The study also offers a prototype model for developing multifaceted PCR assays using intein DNA sequences, and provides a developmental starting point for point-of-care testing in near future.
Objective: The objective of this study was to prove that cow urine distillate (CUD) is a bioenhancer for antimicrobial activity and antiproliferative activity, redistilled CUD (RCUD) as an anticlastogen agent. Methods:The antimicrobial activity of rifampicin with CUD at different concentrations was determined against pathogenic Escherichia coli by well puncture method. The Penicillin and ciprofloxacin in combination with CUD at different/increasing concentrations against pathogenic E. coli culture were also determined by disc diffusion method. Sulforaphane (ACA) as an anticancer agent was extracted from cruciferous vegetables and purified by high-performance liquid chromatography. The Breast cancer cell lines (MCF-7) were treated with anticancer agents along with CUD in increasing concentrations. The anticlastogenic activity of RCUD in human peripheral lymphocytes was tested with clastogens such as manganese dioxide and hexavalent chromium.Results: CUD showed to enhance the antimicrobial activity of rifampicin with 20 µl concentration by well puncture method; penicillin with increasing concentration of up to 80 µl and ciprofloxacin up to 80 µl, respectively, by disc diffusion method. The rate of degeneration of breast cancer cell lines (MCF-7) was increased with increasing concentration of CUD. Clastogen (MnO 2 ) of 10 µl with 200 µl of RCUD showed effective anticlastogenic activity in agarose gel electrophoresis as the activity of clastogen decreased with increasing concentration of RCUD. Conclusion:CUD acts as a bioenhancer to increase antimicrobial and antiproliferative activity. RCUD showed a high level of anticlastogenic activity toward clastogen. Thus, cow urine is found to have special properties that can be used in combination with different therapeutic agents to cure several diseases such as tuberculosis, leprosy, and cancer. Further in vivo and clinical studies are required to confirm its therapeutic efficacy.
The alarming increase in multidrug resistance, which includes Bedaquiline and Delamanid, stumbles success in Tuberculosis treatment outcome. Mycobacterium tuberculosis gains resistance to rifampicin, which is one of the less toxic and potent anti‐TB drugs, through genetic mutations predominantly besides efflux pump mediated drug resistance. In recent decades, scientific interventions are being carried out to overcome this hurdle using novel approaches to save this drug by combining it with other drugs/molecules or by use of high dose rifampicin. This study reports five small molecules namely Ellagic acid, Methyl Stearate, Myoinositol, Rutin, and Shikimic acid that exhibit synergistic inhibitory activity with rifampicin against resistant TB isolates. In‐silico examinations revealed possible blocking of Rv1819c—an ABC transporter efflux pump that was known to confer resistance in M. tuberculosis to rifampicin. The synergistic anti‐TB activity was assessed using a drug combination checkerboard assay. Efflux pump inhibition activity of ellagic acid, myoinositol, and methyl stearate was observed through ethidium bromide accumulation assay in the drug‐resistant M. tuberculosis clinical strains and recombinant Mycobacterium smegmatis expressing Rv1819c in coherence with the significant reduction in the minimum inhibitory concentration of rifampicin. Cytotoxicity of the active efflux inhibitors was tested using in silico and ex vivo methods. Myoinositol and methyl stearate were completely non‐toxic to the hematological and epithelial cells of different organs under ex vivo conditions. Based on these findings, these molecules can be considered for adjunct TB therapy; however, their impact on other drugs of anti‐TB regimen needs to be tested.
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