RESUMO
Background: Heterocyclic analogs of curcumin have a wide range of therapeutic potential and the ability to control the activity of a variety of metabolic enzymes. Methods: 1H-NMR and 13C-NMR spectroscopic techniques were used to determine the structures of synthesized compounds. The agar disc diffusion method and α-amylase inhibition assay were used to examine the antibacterial and anti-diabetic potential of the compounds against α-amylase enzyme inhibitory activity, respectively. DPPH-free radical scavenging and lipid peroxidation inhibition assays were used to assess the in vitro antioxidant potential. Results and Discussion: In this work, nine heterocyclic analogs derived from curcumin precursors under ultrasonic irradiation were synthesized in excellent yields (81.4-93.7%) with improved reaction time. Results of antibacterial activities revealed that compounds 8, and 11 displayed mean inhibition zone of 13.00±0.57, and 19.66±00 mm, respectively, compared to amoxicillin (12.87±1.41 mm) at 500 µg/mL against E. coli, while compounds 8, 11 and 16 displayed mean inhibition zone of 17.67±0.57, 14.33±0.57 and 23.33±00 mm, respectively, compared to amoxicillin (13.75±1.83 mm) at 500 µg/mL against P. aeruginosa. Compound 11 displayed a mean inhibition zone of 11.33±0.57 mm compared to amoxicillin (10.75±1.83 mm) at 500 µg/mL against S. aureus. Compound 11 displayed higher binding affinities of -7.5 and -8.3 Kcal/mol with penicillin-binding proteins (PBPs) and ß-lactamases producing bacterial strains, compared to amoxicillin (-7.2 and -7.9 Kcal/mol, respectively), these results are in good agreement with the in vitro antibacterial activities. In vitro antidiabetic potential on α-amylase enzyme revealed that compounds 11 (IC50=7.59 µg/mL) and 16 (IC50=4.08 µg/mL) have higher inhibitory activities than acarbose (IC50=8.0 µg/mL). Compound 8 showed promising antioxidant inhibition efficacy of DPPH (IC50 = 2.44 g/mL) compared to ascorbic acid (IC50=1.24 g/mL), while compound 16 revealed 89.9±20.42% inhibition of peroxide generation showing its potential in reducing the development of lipid peroxides. In silico molecular docking analysis, results are in good agreement with in vitro biological activity. In silico ADMET profiles suggested the adequate oral drug-likeness potential of the compounds without adverse effects. Conclusion: According to our findings, both biological activities and in silico computational studies results demonstrated that compounds 8, 11, and 16 are promising α-amylase inhibitors and antibacterial agents against E. coli, P. aeruginosa, and S. aureus, whereas compound 8 was found to be a promising antioxidant agent.
RESUMO
INTRODUCTION: Antibiotics are commonly used for the treatment and prevention of bacterial infections. The potency of antibiotics can be affected by factors such as temperature, light, moisture, and storage conditions. Inappropriate storage and transportation of antibiotics may lead to loss of potency earlier than the expiry date. The aim of this study was to determine the potency and associated factors of commonly retailed antibiotics. METHOD: Institution-based cross-sectional study was conducted on commonly retailed antibiotics in pharmacies that are available in Adama, Ethiopia from March 2018 to June 2018. This study focused on commonly ordered antibiotics such as amoxicillin, azithromycin, ciprofloxacin, and ceftriaxone. Antibiotics to be tested were selected by using a simple random sampling technique. Socio-demographic and related data were collected using a semi-structured questionnaire. Antibiotic susceptibility testing was performed using the disc diffusion method as described in the Clinical Laboratory Standard Institute guideline. RESULTS: Mean inhibition zones of amoxicillin, ciprofloxacin, azithromycin, and ceftriaxone were 14.2 ± 4 mm, 30.9 ± 4.2 mm, 17.47 ± 3.83 mm, and 32.7±1.8 respectively. Out of 164 antibiotics tested, 61% passed the potency test. The potency of antibiotics varies across different countries in which 53.7% and 54.6 of antibiotics from India and Ethiopia passed the potency test. All ceftriaxone tested in this study passed the potency test. Factors such as air condition of pharmacy (X2 = 4.27; p = 0.039), source of all antibiotics (X2 = 5.41; p = 0.02), and source of amoxicillin (X2 = 4.73; p = 0.03) were significantly associated with potency of antibiotics. CONCLUSIONS: About 40% of antibiotics tested in the current study did not pass the potency test; this warrants further investigation to identify the magnitude of the problem and its causes at a large scale.
