scholarly journals Systematic analysis of structural and activity relationships between conventional hierarchical and analog series-based scaffolds

RSC Advances ◽  
2017 ◽  
Vol 7 (30) ◽  
pp. 18718-18723 ◽  
Author(s):  
Dagmar Stumpfe ◽  
Dilyana Dimova ◽  
Jürgen Bajorath
Keyword(s):  
Biological Activity ◽  
Systematic Analysis ◽  
Analog Series ◽  
Hierarchical Scaffold

Three pairs of compounds (left) belonging to three different analog series that differ in their biological activity share a single conventional hierarchical scaffold (BM, middle) but have distinct ‘analog series-based’ (ASB) scaffold (right).

scholarly journals Structure-Activity Relationship Analysis of Benzotriazine Analogues as HIV-1 Latency-Reversing Agents

2020 ◽  
Vol 64 (8) ◽  
Author(s):  
Eric S. Sorensen ◽  
Amanda B. Macedo ◽  
Rachel S. Resop ◽  
J. Natalie Howard ◽  
Racheal Nell ◽  
...  
Keyword(s):  
Biological Activity ◽  
Transcriptional Activation ◽  
Transcriptional Activity ◽  
Cell Model ◽  
Systematic Analysis ◽  
Immune Effector ◽  
Relationship Analysis ◽  
Latent Hiv

ABSTRACT “Shock and kill” therapeutic strategies toward HIV eradication are based on the transcriptional activation of latent HIV with a latency-reversing agent (LRA) and the consequent killing of the reactivated cell by either the cytopathic effect of HIV or an arm of the immune system. We have recently found several benzotriazole and benzotriazine analogues that have the ability to reactivate latent HIV by inhibiting signal transducer and activator of transcription 5 (STAT5) SUMOylation and promoting STAT5 binding to the HIV long terminal repeat and increasing its transcriptional activity. To understand the essential structural groups required for biological activity of these molecules, we performed a systematic analysis of >40 analogues. First, we characterized the essential motifs within these molecules that are required for their biological activity. Second, we identified three benzotriazine analogues with similar activity. We demonstrated that these three compounds are able to increase STAT5 phosphorylation and transcriptional activity. All active analogues reactivate latent HIV in a primary cell model of latency and enhance the ability of interleukin-15 to reactivate latent HIV in cells isolated from aviremic participants. Third, this family of compounds also promote immune effector functions in vitro in the absence of toxicity or global immune activation. Finally, initial studies in mice suggest lack of acute toxicity in vivo. A better understanding of the biological activity of these compounds will help in the design of improved LRAs that work via inhibition of STAT5 SUMOylation.

Squaryl group modified phosphoglycolipid analogs as potential modulators of GPR55

2018 ◽  
Vol 54 (61) ◽  
pp. 8470-8473 ◽  
Author(s):  
Feiqing Ding ◽  
Adam T. Guy ◽  
Peter Greimel ◽  
Yoshio Hirabayashi ◽  
Hiroyuki Kamiguchi ◽  
...  
Keyword(s):  
Biological Activity ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Facile Synthesis ◽  
Systematic Analysis ◽  
Structure Activity

We report the facile synthesis of a series of LPGlc analogs, their GPR dependent biological activity and a systematic analysis of the structure–activity relationship in regards to GPR55 modulation.

scholarly journals Tubulin Inhibitors: A Chemoinformatic Analysis Using Cell-Based Data

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2483
Author(s):  
Edgar López-López ◽  
Carlos M. Cerda-García-Rojas ◽  
José L. Medina-Franco
Keyword(s):  
Biological Activity ◽  
Content Analysis ◽  
Cell Lines ◽  
Quantitative Assessment ◽  
Chemical Space ◽  
Rational Approach ◽  
Tubulin Inhibitors ◽  
Narrow Region ◽  
Different Types ◽  
Analog Series

Inhibiting the tubulin-microtubules (Tub-Mts) system is a classic and rational approach for treating different types of cancers. A large amount of data on inhibitors in the clinic supports Tub-Mts as a validated target. However, most of the inhibitors reported thus far have been developed around common chemical scaffolds covering a narrow region of the chemical space with limited innovation. This manuscript aims to discuss the first activity landscape and scaffold content analysis of an assembled and curated cell-based database of 851 Tub-Mts inhibitors with reported activity against five cancer cell lines and the Tub-Mts system. The structure–bioactivity relationships of the Tub-Mts system inhibitors were further explored using constellations plots. This recently developed methodology enables the rapid but quantitative assessment of analog series enriched with active compounds. The constellations plots identified promising analog series with high average biological activity that could be the starting points of new and more potent Tub-Mts inhibitors.

Preparatory Procedures for Electron Microscopic Analysis at the Molecular Level of Resolution

1978 ◽  
Vol 36 (3) ◽  
pp. 516-520
Author(s):  
F.J. Sjostrand
Keyword(s):  
Electron Microscope ◽  
Molecular Level ◽  
Microscopic Analysis ◽  
Resolving Power ◽  
Cellular Structures ◽  
Electron Microscopic ◽  
Systematic Analysis ◽  
Technical Developments ◽  
Thin Sectioning ◽  
Obvious Reason

In the 1940's and 1950's electron microscopy conferences were attended with everybody interested in learning about the latest technical developments for one very obvious reason. There was the electron microscope with its outstanding performance but nobody could make very much use of it because we were lacking proper techniques to prepare biological specimens. The development of the thin sectioning technique with its perfectioning in 1952 changed the situation and systematic analysis of the structure of cells could now be pursued. Since then electron microscopists have in general become satisfied with the level of resolution at which cellular structures can be analyzed when applying this technique. There has been little interest in trying to push the limit of resolution closer to that determined by the resolving power of the electron microscope.

Virus-Like Particles in a Human Breast Cancer: Structural Similarity to Previously Reported Particles

1973 ◽  
Vol 31 ◽  
pp. 378-379
Author(s):  
G. Kasnic ◽  
S. E. Stewart ◽  
C. Urbanski
Keyword(s):  
Breast Cancer ◽  
Biological Activity ◽  
Human Breast Cancer ◽  
Osteogenic Sarcoma ◽  
Human Tumor ◽  
Structural Similarity ◽  
Cell Tumor ◽  
Human Breast ◽  
Human Tumor Cell ◽  
Type Particle

We have reported the maturation of an intracisternal A-type particle in murine plasma cell tumor cultures and three human tumor cell cultures (rhabdomyosarcoma, lung adenocarcinoma, and osteogenic sarcoma) after IUDR-DMSO activation. In all of these studies the A-type particle seems to develop into a form with an electron dense nucleoid, presumably mature, which is also intracisternal. A similar intracisternal A-type particle has been described in leukemic guinea pigs. Although no biological activity has yet been demonstrated for these particles, on morphologic grounds, and by the manner in which they develop within the cell, they may represent members of the same family of viruses.

Effects of Vincristine on Endothelial Microtubules in the Spinal Cord

1976 ◽  
Vol 34 ◽  
pp. 58-59
Author(s):  
John L. Beggs ◽  
John D. Waggener ◽  
Wanda Miller
Keyword(s):  
Spinal Cord ◽  
Biological Activity ◽  
Horseradish Peroxidase ◽  
Transport Mechanism ◽  
Vasogenic Edema ◽  
Vesicular Transport ◽  
Close Proximity

Microtubules (MT) are versatile organelles participating in a wide variety of biological activity. MT involvement in the movement and transport of cytoplasmic components has been well documented. In the course of our study on trauma-induced vasogenic edema in the spinal cord we have concluded that endothelial vesicles contribute to the edema process. Using horseradish peroxidase as a vascular tracer, labeled endothelial vesicles were present in all situations expected if a vesicular transport mechanism was in operation. Frequently,labeled vesicles coalesced to form channels that appeared to traverse the endothelium. The presence of MT in close proximity to labeled vesicles sugg ested that MT may play a role in vesicular activity.

Isothiazol-3(2 H )-ones, Part I: Synthesis, Reactions and Biological Activity

2002 ◽  
Vol 23 (1) ◽  
pp. 79-121 ◽  
Author(s):  
Kathleen Taubert ◽  
Susanne Kraus ◽  
Bärbel Schulze
Keyword(s):  
Biological Activity ◽  
Synthesis Reactions
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