METHODS: The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR). The synthesized compounds were evaluated for their in vitro antimicrobial activity against Gram-positive (B. subtilis), Gram-negative (P. aeruginosa and E. coli) bacterial and fungal (C. albicans and A. niger) strains by tube dilution method using ciprofloxacin, amoxicillin and fluconazole as standards. In-vitro antioxidant and anti-urease screening was done by DPPH assay and indophenol method, respectively. The in-vitro anticancer evaluation was carried out against MCF-7 and HCT116 cancer cell lines using 5-FU as standards.
RESULTS, DISCUSSION AND CONCLUSION: The biological screening results reveal that the compounds T5 (MICBS, EC = 24.7 µM, MICPA, CA = 12.3 µM) and T17 (MICAN = 27.1 µM) exhibited potent antimicrobial activity as comparable to standards ciprofloxacin, amoxicillin (MICCipro = 18.1 µM, MICAmo = 17.1 µM) and fluconazole (MICFlu = 20.4 µM), respectively. The antioxidant evaluation showed that compounds T2 (IC50 = 34.83 µg/ml) and T3 (IC50 = 34.38 µg/ml) showed significant antioxidant activity and comparable to ascorbic acid (IC50 = 35.44 µg/ml). Compounds T3 (IC50 = 54.01 µg/ml) was the most potent urease inhibitor amongst the synthesized compounds and compared to standard thiourea (IC50 = 54.25 µg/ml). The most potent anticancer activity was shown by compounds T2 (IC50 = 3.84 μM) and T7 (IC50 = 3.25 μM) against HCT116 cell lines as compared to standard 5-FU (IC50 = 25.36 μM).
METHODS: We performed a systematic review and network meta-analysis based on randomised controlled trials that compared antifungal agents to placebo or other antifungal agents used in patients undergoing cancer treatment. Relative ranking of antifungal agents was evaluated with surface under the cumulative ranking (SUCRA) probability score. A total of 20 randomised controlled trials (3,215 participants) comparing 11 interventions were included.
RESULTS: Compared with placebo, clotrimazole was ranked the best agent for preventing the incidence of oral candidiasis (risk ratio (RR), 0.21 [95% CI 0.08 to 0.55]; SUCRA = 0.89). Fluconazole was ranked the safest among other antifungal agents (SUCRA = 0.80), whereas clotrimazole (SUCRA = 0.36) and amphotericin B (SUCRA = 0.18) were ranked low for safety. Amphotericin B was associated with highest risk of adverse events (RR, 3.52 [95% CI 1.27 to 9.75]).
CONCLUSION: Clotrimazole is the most effective in preventing oral candidiasis, whereas fluconazole has the most favourable risk-benefit profile in patients undergoing cancer treatment. However, we are unable to recommend clotrimazole as the best choice to prevent oral candidiasis due to unavailability of studies comparing clotrimazole with other antifungal agents.