Unraveling topology-induced shape transformations in dendrimersomes

Much interest has been paid in the last decade on molecular predictors of promiscuity, including molecular weight, log P, molecular complexity, acidity constant and molecular topology, with correlations between promiscuity and those descriptors seemingly being context-dependent. It has been observed that certain therapeutic categories (e.g. mood disorders therapies) display a tendency to include multi-target agents (i.e. selective non-selectivity). Numerous QSAR models based on topological descriptors suggest that the topology of a given drug could be used to infer its therapeutic applications. Here, we have used descriptive statistics to explore the distribution of molecular topology descriptors and other promiscuity predictors across different therapeutic categories. Working with the publicly available ChEMBL database and 14 molecular descriptors, both hierarchical and non-hierchical clustering methods were applied to the descriptors mean values of the therapeutic categories after the refinement of the database (770 drugs grouped into 34 therapeutic categories). On the other hand, another publicly available database (repoDB) was used to retrieve cases of clinically-approved drug repositioning examples that could be classified into the therapeutic categories considered by the aforementioned clusters (111 cases), and the correspondence between the two studies was evaluated. Interestingly, a 3- cluster hierarchical clustering scheme based on only 14 molecular descriptors linked to promiscuity seem to explain up to 82.9% of approved cases of drug repurposing retrieved of repoDB. Therapeutic categories seem to display distinctive molecular patterns, which could be used as a basis for drug screening and drug design campaigns, and to unveil drug repurposing opportunities between particular therapeutic categories.

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Application of Molecular Topology to the Search of Novel NSAIDs: Experimental Validation of Activity

Letters in Drug Design & Discovery ◽

10.2174/157018010791306597 ◽

2010 ◽

Vol 7 (6) ◽

pp. 438-445 ◽

Cited By ~ 14

Author(s):

Maria Galvez-Llompart ◽

Rosa M. Giner ◽

Maria C. Recio ◽

Sanzio Candeletti ◽

Ramon Garcia-Domenech

Keyword(s):

Experimental Validation ◽

Molecular Topology

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On the Contribution of Molecular Topology to Drug Design and Discovery

Current Computer - Aided Drug Design ◽

10.2174/1573409911006040252 ◽

2010 ◽

Vol 6 (4) ◽

pp. 252-268 ◽

Cited By ~ 15

Author(s):

Jorge Galvez ◽

Ramon Garcia-Domenech

Keyword(s):

Drug Design ◽

Molecular Topology

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Development of Structure Information from Molecular Topology for Modeling Chemical and Biological Properties: A Tribute to the Creativity of Lemont Burwell Kier on his 80th Birthday

Current Computer - Aided Drug Design ◽

10.2174/157340912800492393 ◽

2012 ◽

Vol 8 (2) ◽

pp. 93-106 ◽

Cited By ~ 3

Author(s):

Lowell H. Hall

Keyword(s):

Biological Properties ◽

80Th Birthday ◽

Molecular Topology ◽

Structure Information

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Molecular Topology Structure of a Polyketone Modified with Amines

International Polymer Science and Technology ◽

10.1177/0307174x0503200108 ◽

2005 ◽

Vol 32 (1) ◽

pp. 46-56 ◽

Cited By ~ 1

Author(s):

Yu. A. Ol'khov ◽

Yu. N. Smirnov ◽

O. A. Golodkov ◽

G. P. Belov

Keyword(s):

Molecular Topology ◽

Topology Structure

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Nanoparticles as Drug Delivery Systems of RNAi in Cancer Therapy

Molecules ◽

10.3390/molecules26082380 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2380

Author(s):

Diedie Li ◽

Chengzhi Gao ◽

Meiyan Kuang ◽

Minhao Xu ◽

Ben Wang ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Therapeutic Strategy ◽

Target Gene ◽

Treatment Approach ◽

Systemic Delivery ◽

Efficient Delivery ◽

Rnai Therapeutics ◽

Cellular Machinery ◽

Tumor Delivery

RNA interference (RNAi) can mediate gene-silencing by knocking down the expression of a target gene via cellular machinery with much higher efficiency in contrast to other antisense-based approaches which represents an emerging therapeutic strategy for combating cancer. Distinct characters of nanoparticles, such as distinctive size, are fundamental for the efficient delivery of RNAi therapeutics, allowing for higher targeting and safety. In this review, we present the mechanism of RNAi and briefly describe the hurdles and concerns of RNAi as a cancer treatment approach in systemic delivery. Furthermore, the current nanovectors for effective tumor delivery of RNAi therapeutics are classified, and the characteristics of different nanocarriers are summarized.

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The Autophagy Machinery in Human-Parasitic Protists; Diverse Functions for Universally Conserved Proteins

Cells ◽

10.3390/cells10051258 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1258

Author(s):

Hirokazu Sakamoto ◽

Kumiko Nakada-Tsukui ◽

Sébastien Besteiro

Keyword(s):

Membrane Vesicle ◽

Model Organisms ◽

Unicellular Eukaryotes ◽

Current State ◽

Important Challenge ◽

Molecular Machinery ◽

Cellular Machinery ◽

Apparent Reduction ◽

Related Proteins ◽

Genome Projects

Autophagy is a eukaryotic cellular machinery that is able to degrade large intracellular components, including organelles, and plays a pivotal role in cellular homeostasis. Target materials are enclosed by a double membrane vesicle called autophagosome, whose formation is coordinated by autophagy-related proteins (ATGs). Studies of yeast and Metazoa have identified approximately 40 ATGs. Genome projects for unicellular eukaryotes revealed that some ATGs are conserved in all eukaryotic supergroups but others have arisen or were lost during evolution in some specific lineages. In spite of an apparent reduction in the ATG molecular machinery found in parasitic protists, it has become clear that ATGs play an important role in stage differentiation or organelle maintenance, sometimes with an original function that is unrelated to canonical degradative autophagy. In this review, we aim to briefly summarize the current state of knowledge in parasitic protists, in the light of the latest important findings from more canonical model organisms. Determining the roles of ATGs and the diversity of their functions in various lineages is an important challenge for understanding the evolutionary background of autophagy.

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Role of Host-Mediated Post-Translational Modifications (PTMs) in RNA Virus Pathogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms22010323 ◽

2020 ◽

Vol 22 (1) ◽

pp. 323

Author(s):

Ramesh Kumar ◽

Divya Mehta ◽

Nimisha Mishra ◽

Debasis Nayak ◽

Sujatha Sunil

Keyword(s):

Rna Virus ◽

Viral Proteins ◽

Post Translational Modification ◽

Host Proteins ◽

Viral Protein Synthesis ◽

Post Translational Modifications ◽

Small Proteins ◽

Cellular Machinery ◽

Chemical Groups

Being opportunistic intracellular pathogens, viruses are dependent on the host for their replication. They hijack host cellular machinery for their replication and survival by targeting crucial cellular physiological pathways, including transcription, translation, immune pathways, and apoptosis. Immediately after translation, the host and viral proteins undergo a process called post-translational modification (PTM). PTMs of proteins involves the attachment of small proteins, carbohydrates/lipids, or chemical groups to the proteins and are crucial for the proteins’ functioning. During viral infection, host proteins utilize PTMs to control the virus replication, using strategies like activating immune response pathways, inhibiting viral protein synthesis, and ultimately eliminating the virus from the host. PTM of viral proteins increases solubility, enhances antigenicity and virulence properties. However, RNA viruses are devoid of enzymes capable of introducing PTMs to their proteins. Hence, they utilize the host PTM machinery to promote their survival. Proteins from viruses belonging to the family: Togaviridae, Flaviviridae, Retroviridae, and Coronaviridae such as chikungunya, dengue, zika, HIV, and coronavirus are a few that are well-known to be modified. This review discusses various host and virus-mediated PTMs that play a role in the outcome during the infection.

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SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus

Membranes ◽

10.3390/membranes11010064 ◽

2021 ◽

Vol 11 (1) ◽

pp. 64

Author(s):

Jordana Muñoz-Basagoiti ◽

Daniel Perez-Zsolt ◽

Jorge Carrillo ◽

Julià Blanco ◽

Bonaventura Clotet ◽

...

Keyword(s):

Viral Entry ◽

Ebola Virus ◽

Lessons Learned ◽

Productive Infection ◽

Target Cells ◽

Emerging Viruses ◽

Highly Pathogenic ◽

Life Threatening ◽

Pathogenic Viruses ◽

Cellular Machinery

Viruses rely on the cellular machinery to replicate and propagate within newly infected individuals. Thus, viral entry into the host cell sets up the stage for productive infection and disease progression. Different viruses exploit distinct cellular receptors for viral entry; however, numerous viral internalization mechanisms are shared by very diverse viral families. Such is the case of Ebola virus (EBOV), which belongs to the filoviridae family, and the recently emerged coronavirus SARS-CoV-2. These two highly pathogenic viruses can exploit very similar endocytic routes to productively infect target cells. This convergence has sped up the experimental assessment of clinical therapies against SARS-CoV-2 previously found to be effective for EBOV, and facilitated their expedited clinical testing. Here we review how the viral entry processes and subsequent replication and egress strategies of EBOV and SARS-CoV-2 can overlap, and how our previous knowledge on antivirals, antibodies, and vaccines against EBOV has boosted the search for effective countermeasures against the new coronavirus. As preparedness is key to contain forthcoming pandemics, lessons learned over the years by combating life-threatening viruses should help us to quickly deploy effective tools against novel emerging viruses.

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