Medicinal Chemistry

A synthesis of (-)5b and (-)6d according to enzymatic resolution of racemic triazole derivatives 5b and 6d was performed with Lipozyme in 1,4-dioxane, using vinyl benzoate as the acyl donor. The effect of the compounds on TG2 overexpression in human thyroid cancer cell lines cultures at two degrees of malignancyand invasiveness was assessed. The involvement of TG2 in the activation of the apoptotic pathway is also shown. We found that the obtained compounds are able to reduce TG2 overexpression in follicular (FTC-133) and anaplastic (8305C) human thyroid cancer cell lines either in the cytosol, or in the nuclear compartment, activating also the apoptotic pathway. Our data suggest that they may represent new anticancer agents for human thyroid cancer.

Babkground: Psoriasisis a chronic, inflammatory, T-cell mediated autoimmune disease. Many data demonstrating a significantly increased serum levels of both prolactin and IgE in patients with psoriasis vulgaris and reporting an association between their level and psoriasis severity. Existence of prolactin receptors on epidermal keratinocytes provides more support for the hypothesis that prolactin might have a role in the etiogenesis of psoriasis. Objectives of the study: It was aimed to estimate serum prolactin and immunoglobulin E levels in psoriasis vulgaris before and after NB-UVB therapy. Patients and methods: Fifty patients were submitted in this study. Severity of psoriasis was calculated using PASI score. Results: The results showed the following; a statistically significant difference between patients before and after NB-UVB therapy regarding PASI score (P=0.001), a statistically insignificant difference between patients before and after NB-UVB therapy regarding prolactin level (P=0.06), a statistically significant difference between patients before and after NB-UVB therapy regarding IgE level (P=0.0003), a statistically insignificant correlation between PASI score and prolactin level before NB-UVB therapy (P=0.506), a statistically insignificant correlation between PASI score and prolactin level after NB-UVB therapy (P=0.793), a statistically insignificant correlation between PASI score and IgE level before NB-UVB therapy (P=0.074), and a statistically significant correlation between PASI score and IgE level after NB-UVB therapy (P=0.01). Conclusion: The present study concluded that serum prolactin level is elevated in psoriasis vulgaris but there is no correlation of its level with psoriasis severity. Also, serum IgE level is elevated in psoriasis vulgaris and there is a significant correlation between its levels with psoriasis severity

Purpose: Current study involved the design, synthesis and biological evaluation of novel boronic-aurones as anti-tubercular agents targeting inhibition of antigen 85, enzymatic complex involved in synthesis of mycobacterial cell wall. To minimize the probability of a single mutation leading to resistance, it is important to target multiple enzymes implicated in mycobacterium cell wall biosynthesis. Hence, new synthetics were virtually screened against both antigen 85 and enoyl-[acyl-carrier-protein] reductase (InhA).
Methods: Using a structure-based approach, new boronic aurone derivatives were designed to target both antigen 85 and InhA, synthesized and screened for anti-tuberculosis activity against Mycobacterium smegmatis. Minimum inhibitory concentration(MIC) was determined using resazurin-based assay.

Results: Compound CF1 was the most active boronic aurone analog, with MIC of 0.083 mg/mL; followed by CF2 with MIC of 0.100 mg/mL. AL10 and AL11 both exhibited the same MIC of 0.125 mg/mL. Although AL10 and AL11 scored higher in terms of binding affinity during molecular docking, CF2 and CF1 both exhibited higher antimycobacterial activity, showing the importance of hydroxyl groups on aurone core.

Conclusion: This study demonstrates, for the first time, that anti-tuberculosis activity of boronic-aurone derivatives is significant enough, compared to isoniazid, to warrant further investigation.