<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Das, Pronay</style></author><author><style face="normal" font="default" size="100%">Babbar, Palak</style></author><author><style face="normal" font="default" size="100%">Malhotra, Nipun</style></author><author><style face="normal" font="default" size="100%">Sharma, Manmohan</style></author><author><style face="normal" font="default" size="100%">Jachak, Goraknath R.</style></author><author><style face="normal" font="default" size="100%">Gonnade, Rajesh G.</style></author><author><style face="normal" font="default" size="100%">Shanmugam, Dhanasekaran</style></author><author><style face="normal" font="default" size="100%">Harlos, Karl</style></author><author><style face="normal" font="default" size="100%">Yogavel, Manickam</style></author><author><style face="normal" font="default" size="100%">Sharma, Amit</style></author><author><style face="normal" font="default" size="100%">Reddy, D. Srinivasa</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Specific stereoisomeric conformations determine the drug potency of cladosporin scaffold against malarial parasite</style></title><secondary-title><style face="normal" font="default" size="100%">Journal of Medicinal Chemistry</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">JUL</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">61</style></volume><pages><style face="normal" font="default" size="100%">5664-5678</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;The dependence of drug potency on diastereomeric configurations is a key facet. Using a novel general divergent synthetic route for a three-chiral center antimalarial natural product cladosporin, we built its complete library of stereoisomers (cladologs) and assessed their inhibitory potential using parasite-, enzyme-, and structure-based assays. We show that potency is manifest via tetrahyropyran ring conformations that are housed in the ribose binding pocket of parasite lysyl tRNA synthetase (KRS). Strikingly, drug potency between top and worst enantiomers varied 500-fold, and structures of KRS-cladolog complexes reveal that alterations at C3 and C10 are detrimental to drug potency whereas changes at C3 are sensed by rotameric flipping of glutamate 332. Given that scores of antimalarial and anti-infective drugs contain chiral centers, this work provides a new foundation for focusing on inhibitor stereochemistry as a facet of antimicrobial drug development.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">13</style></issue><custom3><style face="normal" font="default" size="100%">Foreign</style></custom3><custom4><style face="normal" font="default" size="100%">6.259</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Babbar, Palak</style></author><author><style face="normal" font="default" size="100%">Das, Pronay</style></author><author><style face="normal" font="default" size="100%">Manickam, Yogavel</style></author><author><style face="normal" font="default" size="100%">Mankad, Yash</style></author><author><style face="normal" font="default" size="100%">Yadav, Swati</style></author><author><style face="normal" font="default" size="100%">Parvez, Suhel</style></author><author><style face="normal" font="default" size="100%">Sharma, Amit</style></author><author><style face="normal" font="default" size="100%">Reddy, Srinivasa</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Design, synthesis, and structural analysis of cladosporin-based inhibitors of malaria parasites</style></title><secondary-title><style face="normal" font="default" size="100%">ACS Infectious Diseases</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2021</style></year><pub-dates><date><style  face="normal" font="default" size="100%">JUL</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">7</style></volume><pages><style face="normal" font="default" size="100%">1777–1794</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;span style=&quot;font-family: Georgia, serif; font-size: 17px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400; background-color: rgb(244, 244, 244);&quot;&gt;Here we have described a systematic structure activity relationship (SAR) of a set of compounds inspired from cladosporin, a tool compound that targets parasite (&lt;/span&gt;&lt;i style=&quot;outline: none; font-family: Georgia, serif; font-size: 17px; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400; background-color: rgb(244, 244, 244);&quot;&gt;Plasmodium falciparum&lt;/i&gt;&lt;span style=&quot;font-family: Georgia, serif; font-size: 17px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400; background-color: rgb(244, 244, 244);&quot;&gt;) lysyl tRNA synthetase (KRS). Four sets of analogues, synthesized based on point changes in the chemical scaffold of cladosporin and other logical modifications and hybridizations, were assessed using high throughput enzymatic and parasitic assays along with&amp;nbsp;&lt;/span&gt;&lt;i style=&quot;outline: none; font-family: Georgia, serif; font-size: 17px; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400; background-color: rgb(244, 244, 244);&quot;&gt;in vitro&lt;/i&gt;&lt;span style=&quot;font-family: Georgia, serif; font-size: 17px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400; background-color: rgb(244, 244, 244);&quot;&gt;&amp;nbsp;pharmacokinetics. Co-crystallization of the most potent compound in our series (&lt;/span&gt;&lt;span style=&quot;outline: none; font-weight: bolder; font-family: Georgia, serif; font-size: 17px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; background-color: rgb(244, 244, 244);&quot;&gt;CL-2&lt;/span&gt;&lt;span style=&quot;font-family: Georgia, serif; font-size: 17px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400; background-color: rgb(244, 244, 244);&quot;&gt;) with&amp;nbsp;&lt;/span&gt;&lt;i style=&quot;outline: none; font-family: Georgia, serif; font-size: 17px; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400; background-color: rgb(244, 244, 244);&quot;&gt;Pf&lt;/i&gt;&lt;span style=&quot;font-family: Georgia, serif; font-size: 17px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400; background-color: rgb(244, 244, 244);&quot;&gt;KRS revealed its structural basis of enzymatic binding and potency. Further, we report that&amp;nbsp;&lt;/span&gt;&lt;span style=&quot;outline: none; font-weight: bolder; font-family: Georgia, serif; font-size: 17px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; background-color: rgb(244, 244, 244);&quot;&gt;CL-2&lt;/span&gt;&lt;span style=&quot;font-family: Georgia, serif; font-size: 17px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400; background-color: rgb(244, 244, 244);&quot;&gt;&amp;nbsp;has performed better than cladosporin in terms of metabolic stability. It thus represents a new lead for further optimization toward the development of antimalarial drugs. Collectively, along with a lead compound, the series offers insights on how even the slightest chemical modification might play an important role in enhancing or decreasing the potency of a chemical scaffold.&lt;/span&gt;&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">6</style></issue><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">&lt;p&gt;Foreign&lt;/p&gt;</style></custom3><custom4><style face="normal" font="default" size="100%">5.084</style></custom4></record></records></xml>