scholarly journals Erratum: Corrigendum: Identification of Leishmania donovani Topoisomerase 1 inhibitors via intuitive scaffold hopping and bioisosteric modification of known Top 1 inhibitors

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Rajinikanth Mamidala ◽  
Papiya Majumdar ◽  
Kunal Kumar Jha ◽  
Chandramohan Bathula ◽  
Rahul Agarwal ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Scaffold Hopping ◽  
Topoisomerase 1

scholarly journals Identification of Leishmania donovani Topoisomerase 1 inhibitors via intuitive scaffold hopping and bioisosteric modification of known Top 1 inhibitors

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Rajinikanth Mamidala ◽  
Papiya Majumdar ◽  
Kunal Kumar Jha ◽  
Chandramohan Bathula ◽  
Rahul Agarwal ◽  
...  
Keyword(s):  
Binding Sites ◽  
Leishmania Donovani ◽  
Scaffold Hopping ◽  
Cos7 Cell ◽  
Single Digit ◽  
Docking Analysis ◽  
Dna Relaxation ◽  
Topoisomerase 1 ◽  
Inhibition Experiment ◽  
Molecular Library

Abstract A library of arylidenefuropyridinediones was discovered as potent inhibitors of Leishmania donovani Topoisomerase 1 (LdTop1) where the active molecules displayed considerable inhibition with single digit micromolar EC50 values. This molecular library was designed via intuitive scaffold hopping and bioisosteric modification of known topoisomerase 1 inhibitors such as camptothecin, edotecarin and etc. The design was rationalized by molecular docking analysis of the compound prototype with human topoisomerase 1 (HTop1) and Leishmania donovani topoisomerase 1(LdTop1). The most active compound 4 displayed no cytotoxicity against normal mammalian COS7 cell line (~100 fold less inhibition at the EC50). Similar to camptothecin, 4 interacted with free LdTop1 as observed in the preincubation DNA relaxation inhibition experiment. It also displayed anti-protozoal activity against Leishmania donovani promastigote. Crystal structure investigation of 4 and its molecular modelling with LdTop1 revealed putative binding sites in the enzyme that could be harnessed to generate molecules with better potency.

Natural and synthetic indirubins as potent and selective inhibitors of the protozoan parasite Leishmania donovani

Planta Medica ◽  
2007 ◽  
Vol 73 (09) ◽  
Author(s):  
E Xingi ◽  
D Smirlis ◽  
S Bisti ◽  
V Myrianthopoulos ◽  
P Magiatis ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Protozoan Parasite ◽  
Selective Inhibitors ◽  
Parasite Leishmania ◽  
Natural And Synthetic

AutoLinker: Automatic Fragment Linking with Deep Conditional Transformer Neural Networks

2020 ◽  
Author(s):  
Yuyao Yang ◽  
Shuangjia Zheng ◽  
Shimin Su ◽  
Jun Xu ◽  
Hongming Chen
Keyword(s):  
Neural Networks ◽  
Drug Discovery ◽  
Drug Design ◽  
State Of The Art ◽  
The State ◽  
Generative Model ◽  
Lead Optimization ◽  
Scaffold Hopping ◽  
Reference Models ◽  
Lead Generation

Fragment based drug design represents a promising drug discovery paradigm complimentary to the traditional HTS based lead generation strategy. How to link fragment structures to increase compound affinity is remaining a challenge task in this paradigm. Hereby a novel deep generative model (AutoLinker) for linking fragments is developed with the potential for applying in the fragment-based lead generation scenario. The state-of-the-art transformer architecture was employed to learn the linker grammar and generate novel linker. Our results show that, given starting fragments and user customized linker constraints, our AutoLinker model can design abundant drug-like molecules fulfilling these constraints and its performance was superior to other reference models. Moreover, several examples were showcased that AutoLinker can be useful tools for carrying out drug design tasks such as fragment linking, lead optimization and scaffold hopping.

Serum Lipid Profile in Diffuse versus Limited Systemic Sclerosis Data from the SASS cohort

2018 ◽  
Vol 69 (2) ◽  
pp. 403-406
Author(s):  
Codrina Ancuta ◽  
Cristina Pomirleanu ◽  
Cristina Iordache ◽  
Magda Ecaterina Antohe ◽  
Rodica Chirieac ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Lipid Profile ◽  
Total Cholesterol ◽  
Serum Lipid ◽  
Total Cholesterol Level ◽  
Cross Sectional Study ◽  
Serum Lipid Profile ◽  
Serum Triglycerides ◽  
Cross Sectional ◽  
Topoisomerase 1

Data about lipoprotein changes and their link with cardiovascular disease and atherosclerosis in systemic sclerosis (SSc) are still challenging. We aimed to evaluate serum lipid profile of patients with SSc and to identify potential relation with different disease specific characteristics (clinical, serological, inflammatory tests) in a cross-sectional study. Standard assessments comprised SSc-related parameters (disease subtype, clinical spectrum, immunological tests) and lipid metabolism (total cholesterol and fractions, triglycerides). Impaired lipid profile (low serum HDL- and high LDL-cholesterol, increased serum triglycerides, slightly modification in total cholesterol level) significantly correlated with diffuse SSc, activity (EUSTAR) and severity (MEDSGER), as well as seropositivity for specific antibodies (anti-centromere and anti-topoisomerase 1). The dyslipidemic profile might represent a pathobiological pathway for atherosclerosis in SSc.

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