Differential induction of Leishmania donovani bi-subunit topoisomerase I–DNA cleavage complex by selected flavones and camptothecin: activity of flavones against camptothecin-resistant topoisomerase I

Emergence of the bi-subunit topoisomerase I in the kinetoplastid family (Trypanosoma and Leishmania) has brought a new twist in topoisomerase research related to evolution, functional conservation and preferential sensitivities to the specific inhibitors of type IB topoisomerase family. In the present study, we describe that naturally occurring flavones baicalein, luteolin and quercetin are potent inhibitors of the recombinant Leishmania donovani topoisomerase I. These compounds bind to the free enzyme and also intercalate into the DNA at a very high concentration (300 µM) without binding to the minor grove. Here, we show that inhibition of topoisomerase I by these flavones is due to stabilization of topoisomerase I–DNA cleavage complexes, which subsequently inhibit the religation step. Their ability to stabilize the covalent topoisomerase I–DNA complex in vitro and in living cells is similar to that of the known topoisomerase I inhibitor camptothecin (CPT). However, in contrast to CPT, baicalein and luteolin failed to inhibit the religation step when the drugs were added to pre-formed enzyme substrate binary complex. This differential mechanism to induce the stabilization of cleavable complex with topoisomerase I and DNA by these selected flavones and CPT led us to investigate the effect of baicalein and luteolin on CPT-resistant mutant enzyme LdTOP1Δ39LS lacking 1–39 amino acids of the large subunit [B. B. Das, N. Sen, S. B. Dasgupta, A. Ganguly and H. K. Majumder (2005) J. Biol. Chem. 280, 16335–16344]. Baicalein and luteolin stabilize duplex oligonucleotide cleavage with LdTOP1Δ39LS. This observation was further supported by the stabilization of in vivo cleavable complex by baicalein and luteolin with highly CPT-resistant L.donovani strain. Taken together, our data suggest that the interacting amino acid residues of topoisomerase I may be partially overlapping or different for flavones and CPT. This study illuminates new properties of the flavones and provide additional insights into the ligand binding properties of L.donovani topoisomerase I

The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis

Background: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. Methods: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. Results and Conclusion: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events

Analysis of drug induced covalent topoisomerase I–DNA complex formation in promastigotes by KCl-SDS precipitation assay

<p><b>Copyright information:</b></p><p>Taken from "Differential induction of bi-subunit topoisomerase I–DNA cleavage complex by selected flavones and camptothecin: activity of flavones against camptothecin-resistant topoisomerase I"</p><p>Nucleic Acids Research 2006;34(4):1121-1132.</p><p>Published online 18 Feb 2006</p><p>PMCID:PMC1373691.</p><p>© The Author 2006. Published by Oxford University Press. All rights reserved</p> Exponentially growing promastigotes (5 × 10 cells/ml) were labeled with [H]thymidine at 22°C for 24 h and then treated with different concentrations of drugs as indicated. Parts of the labeled cells were treated with DHBA (150 µM) for 10 min before the addition of different concentration of baicalein as indicated. SDS-K precipitable complex were measured as described in Materials and Methods. Experiments were performed three times and representative data from one set of experiments are expressed as means ± SD. Variations among different set of experiments wer

Abstracts of National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020

This book presents the abstracts of the papers presented to the Online National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020 (RDMPMC-2020) held on 26th and 27th August 2020 organized by the Department of Metallurgical and Materials Science in Association with the Department of Production and Industrial Engineering, National Institute of Technology Jamshedpur, Jharkhand, India. Conference Title: National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020Conference Acronym: RDMPMC-2020Conference Date: 26–27 August 2020Conference Location: Online (Virtual Mode)Conference Organizer: Department of Metallurgical and Materials Engineering, National Institute of Technology JamshedpurCo-organizer: Department of Production and Industrial Engineering, National Institute of Technology Jamshedpur, Jharkhand, IndiaConference Sponsor: TEQIP-