亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

In-silico Designing, ADMET Analysis, Synthesis and Biological Evaluation of Novel Derivatives of Diosmin Against Urease Protein and Helicobacter pylori Bacterium

尿素酶 生物信息学 地奥司明 化学 细菌 微生物学 幽门螺杆菌 计算生物学 生物化学 抗氧化剂 生物 基因 遗传学 类黄酮
作者
Ritu Kataria,Anurag Khatkar
出处
期刊:Current Topics in Medicinal Chemistry [Bentham Science Publishers]
卷期号:19 (29): 2658-2675 被引量:8
标识
DOI:10.2174/1568026619666191114123452
摘要

Designing drug candidates against the urease enzyme, which has been found responsible for many pathological disorders in human beings as well as in animals, was done by insilico means.Studies were carried out on a designed library of diosmin derivatives with the help of Schrodinger's maestro package of molecular docking software against a crystallographic complex of plant enzyme Jack bean urease (PDB ID: 3LA4). Best twelve derivatives of diosmin were selected for synthesis by considering their interaction energy along with docking score and were further investigated for antioxidant, urease inhibitory and Anti-H. pylori activity by in- vitro method along with ADMET analysis.In-vitro results of series concluded compounds D2a, D2d and D7 (IC50 12.6 ± 0.002, 14.14 ± 0.001 and 15.64 ± 0.012 µM respectively in urease inhibition and 5.195 ± 0.036, 5.39 ± 0.020 and 5.64± 0.005 µM in antioxidant behavior against DPPH) were found to be significantly potent with excellent docking score -11.721, -10.795, -10.188 and binding energy -62.674, -63.352, -56.267 kJ/ mol as compared to standard drugs thiourea and acetohydroxamic acid (-3.459, -3.049 and -21.156 kJ/mol and - 17.454 kJ/mol) whereas compounds D2b, D5b, D5d and D6 were found moderate in urease inhibitory activity.Selected candidates from the outcome of in-vitro urease inhibitory were further examined for anti- H. pylori activity by a well diffusion method against H. pylori bacterium (DSM 4867). Compound D2a showed good anti-H. Pylori activity with a zone of inhibition 10.00 ± 0.00 mm and MIC value 500µg/mL as compared to standard drug acetohydroxamic acid having a zone of inhibition 9.00 ± 0.50mm and MIC 1000µg/mL. In- silico studies played an important role in designing the potent ligands against urease protein as well as in explaining the binding pattern of designed and synthesized ligand within the active pocket of jack bean urease protein. ADMET studies were also carried out to check the drug similarity of designed compounds by the means of quikprop module of molecular docking software. Hence, the present investigation studies will provide a new vision for the discovery of potent agents against H. pylori and urease associated diseases.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
10秒前
科研通AI5应助James采纳,获得10
45秒前
啦啊啦啦啦应助柏风华采纳,获得20
56秒前
CodeCraft应助科研通管家采纳,获得10
1分钟前
bc应助科研通管家采纳,获得20
1分钟前
柏风华完成签到,获得积分10
2分钟前
2分钟前
2分钟前
知行者完成签到 ,获得积分10
2分钟前
Jasmineyfz完成签到 ,获得积分10
3分钟前
andrele应助科研通管家采纳,获得10
3分钟前
科研通AI2S应助科研通管家采纳,获得10
3分钟前
科研通AI2S应助科研通管家采纳,获得10
3分钟前
yinlao完成签到,获得积分10
4分钟前
大模型应助南瓜采纳,获得10
4分钟前
bc应助科研通管家采纳,获得30
5分钟前
bc应助科研通管家采纳,获得30
5分钟前
bc应助科研通管家采纳,获得30
5分钟前
5分钟前
南瓜发布了新的文献求助10
5分钟前
6分钟前
南瓜完成签到,获得积分10
6分钟前
6分钟前
James发布了新的文献求助10
6分钟前
小蘑菇应助科研通管家采纳,获得10
7分钟前
andrele应助科研通管家采纳,获得10
7分钟前
高数数完成签到 ,获得积分10
8分钟前
8分钟前
moroa完成签到,获得积分10
9分钟前
___淡完成签到 ,获得积分10
9分钟前
科研通AI2S应助科研通管家采纳,获得10
9分钟前
Eason完成签到,获得积分10
10分钟前
史前巨怪完成签到,获得积分10
10分钟前
ycw7777完成签到,获得积分10
11分钟前
幽默发夹发布了新的文献求助10
12分钟前
幽默发夹完成签到,获得积分10
12分钟前
12分钟前
哇哈哈发布了新的文献求助10
12分钟前
Jasper应助哇哈哈采纳,获得10
13分钟前
科研通AI2S应助科研通管家采纳,获得10
13分钟前
高分求助中
Les Mantodea de Guyane Insecta, Polyneoptera 2500
Mobilization, center-periphery structures and nation-building 600
Technologies supporting mass customization of apparel: A pilot project 520
Introduction to Strong Mixing Conditions Volumes 1-3 500
Fine Chemicals through Heterogeneous Catalysis 430
China—Art—Modernity: A Critical Introduction to Chinese Visual Expression from the Beginning of the Twentieth Century to the Present Day 430
Multichannel rotary joints-How they work 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3795558
求助须知:如何正确求助?哪些是违规求助? 3340610
关于积分的说明 10300696
捐赠科研通 3057127
什么是DOI,文献DOI怎么找? 1677500
邀请新用户注册赠送积分活动 805424
科研通“疑难数据库(出版商)”最低求助积分说明 762529