Synthesis,Urease Inhibition and Molecular Modelling Studies of Novel Derivatives of the Naturally Occurring b-Amyrenone

Urease enzyme(UE)has been reported to be a potent virulence factor for Helicobacter pylori(HP)bacteria indicated to be responsible for various gastrointestinal diseases.Therefore,the spread of HP,currently regarded by the World Health Organization as a class 1 carcinogen,could be better controlled by targeting UE.It is in this line that we have synthesized three new derivatives(2–4)of the naturally occurring olean-12-en-3-one(1),which was previously isolated from the figs of Ficus vallis-choudae Delile(Moraceae).Among the synthesized compounds,3 and 4 contain an indole moiety.Their structures were unambiguously assigned by spectroscopic and spectrometric techniques(1D-NMR,2D-NMR and MS).The starting material and the synthesized compounds were screened for UE inhibition activity,and showed significant activities with IC50 values ranging from 14.5 to 24.6 lM,with compound(1)being the most potent as compared to the positive control thiourea(IC50=21.6 lM).Amongst the synthetic derivatives,compound 4 was the most potent(IC50-=17.9 lM),while the others showed activities close to that of the control.In addition,molecular docking study of target compounds 2–4 was performed in an attempt to explore their binding mode for the design of more potent UE inhibitors.

<i>Fusarium lini</i>Potential for the Biotransformation of Norandrostenedione and Evaluation of Urease and Chymotrypsin Properties of the Transformed Products

Several androgenic steroids have been biotransformed by fungi into metabolites with numerous biological properties. Incubation of norandrostenedione (1) with Fusarium lini NRRL 2204 was carried out for the first time, yielding two new metabolites, 3,7β-dihydroxy-19-norandrost-1,3,5-trien-17-one (3) and 6α,10β,17β-trihydroxy-19-nor-4-androsten-3-one (4), along with three known compounds, 3-hydroxy-19-norandrost-1,3,5-trien-17-one (2), 10β, 17β-dihydroxy-19-nor-4-androsten-3-one (5) and 10β-hydroxy-19-nor-4- androsten-3,17-dione (6). Their structures were elucidated by extensive spectroscopic analyses, including 1D-, 2D-NMR, and HR-MS experiments. Substrate 1 and its derivatives 2-6 were evaluated in vitro for their urease and chymotrypsin inhibitory properties. Compounds 2 and 3 were found to have strong urease activity with IC50 = 23.7 ± 0.17 and 10.2 ± 0.28 μm, respectively, as compared to the standard drug thiourea (IC50 = 21.6 ± 0.12 μm). Compounds 4, 5 and 6 showed good chymotrypsin activity with IC50 values of 6.4 ± 0.19, 15.6 ± 0.46 and 18.4 ± 0.65 μm, respectively, as compared to standard chymostatin with IC50 = 5.7 ± 0.14 μm. These transformed metabolites may form the basis for the future development of new drugs against ulcer, inflammation, bacterial and viral diseases.

Development of bis-thiobarbiturates as successful urease inhibitors and their molecular modeling studies

Bis-thiobarbiturate derivatives 1-15 have been synthesized, characterized by 1HNMR and El-MS and screened for urease inhibition. All compounds showed various degree of urease inhibitory activity with iC50 values ranging 7.45 ± 0.12 - 74.24 ± 0.81 μmol/L while the standard thiourea behaved normally （ICso = 21.10 ±0.12）. Compounds I （IC50= 7.45 ± 0.12 ]μmol/L）, 9 （IC50 =18,17 ± 1.03 bmol/L） and 13 （IC50= 8.61 ± 0.45 bmol/L） showed excellent urease inhibitory activity in the series. Molecular modeling studies were performed to understand the binding site with the bimetallic nickel center of the enzyme. Structure-activity relationship has also been established for these compounds. This study identified bis- thiobarbiturate as a novel class of urease inhibitors.

New antiglycation and enzyme inhibitors from Parmotrema cooperi

Lichens are unique individuals which have been widely used in traditional medicines. This study was focused on the bioassayguided phytochemical investigation, and bioactivity evaluation on a lichens species, Parmotrema cooperi. This first bioassaydirected chemical study on P. cooperi has led to the isolation of ethyl heamatomate （1）, atraric acid （2）, ethyl orsellinate （3）, orsellinic acid （4）, lecanoric acid （5）, gyrophoric acid （6）, and licanorin （7）. The structures of 1-7 were mainly elucidated from spectroscopic methods including 1D, and 2D NMR spectroscopy, and mass spectrometry. These compounds were evaluated for their antiglycation, urease, a-chymotrypsin, and β-glucoronidase inhibitory activities. Few of the phenolic compounds showed significant, while most of them showed good inhibition of protein glycation, and urease activities.