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Title: Synthesis, Characterization of Novel Curcumin Analogs and Their Biological Activities
Authors: Ahmed, Mahmood
Keywords: Chemistry
Issue Date: 2018
Publisher: University of the Punjab , Lahore
Abstract: Curcumin has shown large number of pharmacological properties against different phenotypes of various disease models. Different synthetic routes have been employed to develop its various derivatives for diverse biological functions. In this study Schiff bases, pyrazoles, pyrimidines and sulfonamides bearing curcumin scaffold were synthesized to investigate their pharmacological effects. The structures of newly synthesized compounds were described by IR, MS, 1H NMR, 13C NMR spectral data and elemental analysis. Antibacterial and antifungal activities were evaluated for compounds (3-14) with Ciprofloxacin, Nystatin and Ketoconazole using disc diffusion method and minimum inhibitory concentration values were determined by 96-well plate assay method. Our studies showed that compound 3 has promising antibacterial (MIC: 15.63-31.25 µg/mL) while compound 5 (MIC: 15.63-250 µg/mL) has better antifungal activity as compared to reference drugs. Similarly the combination of more potent compounds 3 and 5 with Ciprofloxacin and Nystatin respectively gave significant synergic effect (FIC index value ≤ 1). The anti-inflammatory and antinociceptive activities of compounds (3-25) were also evaluated with Indomethacin and Diclofenac sodium in experimental animal models respectively. Compound 20, 21 and 25 exhibited relatively higher prevention of writhing episodes than any other compound with antinociceptive activity of 73.2, 74.9 and 71.8 % respectively whereas compound 3 showed highest anti-inflammatory activity (82.0 % paw edema inhibition). Cyclooxygenase-2 (COX-2) enzyme inhibition was evaluated with these synthesized compounds (3-25) through in vitro cyclooxygenase assays. COX-2 inhibition assays result revealed that compound 25 (75.3 %) was the most active compound. Molecular docking vi studies were also performed to identify the plausible binding mode of these compounds with COX-2. Urease enzyme inhibition was also evaluated through in vitro assays and inhibition assays result revealed that compound 24 was found to be more potent (IC50 = 2.44±0.07 µM) among the tested compounds (3-25). The compounds with diazine ring system showed better urease inhibition (IC50 = 11.43±0.21-19.63±0.28 µM) than the standard urease inhibitor thiourea (IC50 = 22.61±0.23 µM). Kinetic data revealed that compounds 5-7, 24 were competitive inhibitors with Ki values 20.0, 19.87, 20.23 and 19.11 µM respectively. Compounds 26-47 were screened for in vitro carbonic anhydrase-I (human, hCAI) and carbonic anhydrase-II (bovine, bCAII) inhibition assay. Compound 26 showed the Ki 0.99 µM and had more inhibitory activity on hCA-I than Acetazolamide (AZZ). From kinetic studies the Ki values of compound 26, 28 and 42 towards bCAII were 0.71, 0.67 and 0.71 µM respectively. Compound 28 has comparable Ki to AZZ (0.63 µM) towards bCAII. Compounds 48-53 were screened for antibacterial activity, compounds 48 with isoxazole moiety have moderate antibacterial activity against both the gram positive and gram negative bacteria with highest zone of inhibition (18.7 mm) against S. aureus with AI value 56.2 % when compared with Ciprofloxacin having MIC > 500 µg/mL. While the rest of compounds in this series showed poor antibacterial activity.
Gov't Doc #: 19164
Appears in Collections:PhD Thesis of All Public / Private Sector Universities / DAIs.

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