Combinatorial Design of Molecule using Activity-Linked Substructural Topological Information as Applied to Antitubercular Compounds

2018 ◽  
Vol 15 (1) ◽  
pp. 67-81 ◽  
Author(s):  
Chandan Raychaudhury ◽  
Md. Imbesat Hassan Rizvi ◽  
Debnath Pal
Keyword(s):  
Biological Activities ◽  
Combinatorial Design ◽  
Combinatorial Structure ◽  
Potential Drug ◽  
Structure Generation ◽  
Topological Information ◽  
Active Compounds ◽  
Antitubercular Drugs ◽  
Topological Distance ◽  
Drug Molecules

Background: Generating a large number of compounds using combinatorial methods increases the possibility of finding novel bioactive compounds. Although some combinatorial structure generation algorithms are available, any method for generating structures from activity-linked substructural topological information is not yet reported. Objective: To develop a method using graph-theoretical techniques for generating structures of antitubercular compounds combinatorially from activity-linked substructural topological information, predict activity and prioritize and screen potential drug candidates. </P><P> Methods: Activity related vertices are identified from datasets composed of both active and inactive or, differently active compounds and structures are generated combinatorially using the topological distance distribution associated with those vertices. Biological activities are predicted using topological distance based vertex indices and a rule based method. Generated structures are prioritized using a newly defined Molecular Priority Score (MPS). Results: Studies considering a series of Acid Alkyl Ester (AAE) compounds and three known antitubercular drugs show that active compounds can be generated from substructural information of other active compounds for all these classes of compounds. Activity predictions show high level of success rate and a number of highly active AAE compounds produced high MPS score indicating that MPS score may help prioritize and screen potential drug molecules. A possible relation of this work with scaffold hopping and inverse Quantitative Structure-Activity Relationship (iQSAR) problem has also been discussed. The proposed method seems to hold promise for discovering novel therapeutic candidates for combating Tuberculosis and may be useful for discovering novel drug molecules for the treatment of other diseases as well.

Structure and Activity of Pentacyclic Triterpenes Codrugs. A Review

2021 ◽  
Vol 21 ◽  
Author(s):  
Justyna Żwawiak ◽  
Anna Pawełczyk ◽  
Dorota Olender ◽  
Lucjusz Zaprutko
Keyword(s):  
Biological Activities ◽  
Anticancer Activities ◽  
Drug Molecule ◽  
Pentacyclic Triterpene ◽  
Formation Pathway ◽  
Chemical Systems ◽  
Drug Molecules ◽  
Wide Range ◽  
Anti Hiv ◽  
Structure And Activity

: Triterpenes are a wide and important group of compounds that have several promising pharmacological properties, such as hepatoprotective, anti-inflammatory, anti-HIV, antioxidant, or anticancer activities. Such potent substances can be successfully incorporated in more complex chemical systems e.g. codrugs or pro-drugs that have better pharmacological profile. The codrug is connected with a drug formation pathway to chemically cohere at least two drug molecules to improve positive therapeutic efficiency or decrease side effects. The codrug can be cleaved in the organism to generate effective compounds previously used as substrates. This article presents an overview of codrugs that consist of pentacyclic triterpene moiety that is chosen as a basic codrug moiety due to their wide range of vital activities and another drug molecule fragment. It was found that triterpenoid codrugs are characterized by a wide range of biological activities. However, most of them have anticancer potency.

Medicinal Chemistry of Alternative Therapeutics: Novelty and Hopes with Genus Ammannia

2019 ◽  
Vol 19 (10) ◽  
pp. 784-794 ◽  
Author(s):  
Harish C. Upadhyay
Keyword(s):  
Traditional Medicine ◽  
Biological Activities ◽  
World Health ◽  
Biologically Relevant ◽  
Traditional Medicines ◽  
Drug Molecules ◽  
Health Organization ◽  
Tract Infections ◽  
Pharmacologically Active ◽  
Herbal Formulations

The plants have formed the basis of folklore remedy since the beginning of human civilization. The cumulative human endeavor and experience over a period of thousands of years developed into well to organize traditional medicine systems viz. Ayurvedic, Unani, Chinese amongst others. Across the world, traditional medicine is either the mainstay of health care or serves as a complement to modern drugs. In view of worldwide use of traditional medicines, World Health Organization launched ‘WHO-Traditional Medicine Strategy 2014-2023’ for the development of strong policies regarding knowledge-base, safety, quality-control and effectiveness of traditional/alternative therapeutics for national health systems. Besides their use in traditional medicine, plants have always been a good source of modern drug/pharmacologically active molecules. More than half of the modern pharmaceuticals are either plant isolates or their derivatives. The plant-based drugs are not only effective, but have better compatibility with human biological systems because of more biologically relevant chemistry, hence lesser side effects. Some of the species of genus Ammannia (Lythraceae) have been reported for their magical medicinal values. Many herbal formulations containing Ammannia spp. have been patented for treatment of serious diseases/disorders like cancer, spinal disease, human female infertility, chronic tonsillitis, pelvic inflammatory disease, treatment of bladder stones, urinary tract infections, dermatitis etc. The uses of Ammannia spp. in traditional medicine have been further verified by the biological activities of their extracts as well as isolation of bioactive phytomolecules. The current review provides details about Ammannia spp.; its use in folklore remedy, herbal formulations, biological activities of extracts, isolation of bioactive phytomolecules and SAR study of semi-synthetic derivatives to analyze the possibility of new drug molecules of plant origin.

Muramyl-dipeptide analogues: Synthesis and biological activities

1988 ◽  
Vol 53 (11) ◽  
pp. 2897-2906 ◽  
Author(s):  
Jan Ježek ◽  
Milan Zaoral ◽  
Miloš Buděšínský ◽  
Jiří Günther ◽  
Jiří Rotta
Keyword(s):  
Biological Activities ◽  
Muramyl Dipeptide ◽  
Delayed Hypersensitivity ◽  
Test Compound ◽  
Active Compounds ◽  
Dipeptide Analogues ◽  
Pyrogenic Activity

In the search for immunoadjuvant active compounds without pyrogenic activity we prepared N-Ac-norMur-L-Abu-D-Gln-O-Bu (V), N-Ac-Mur-L-Abu-D-Gln-O-Bu (VII) and their respective α-benzylglycosides VI and VIII. All the prepared compounds are nonpyrogenic. In the delayed hypersensitivity test, compound V is inactive, VI is comparable to MDP, VII is more and VIII is less active than MDP.

scholarly journals Green Synthesis andIn VitroBiological Evaluation of Heteroaryl Chalcones and Pyrazolines of Medicinal Interest

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Vishal Banewar
Keyword(s):  
Green Synthesis ◽  
Elemental Analysis ◽  
Broad Spectrum ◽  
Spectroscopic Data ◽  
Heterocyclic Compounds ◽  
Biological Activities ◽  
Biological Evaluation ◽  
Active Compounds

Pyrazolines are well known and important nitrogen containing 5-membered heterocyclic compounds. In the present investigation, a series of various heteroaryl chalcones and pyrazolines were synthesized by condensing formylquinolines with diverse ketones. The newly synthesized 2-pyrazolines were characterized on the basis of elemental analysis and spectroscopic data. All of the newly synthesized target compounds were selected by the NCI forin vitrobiological evaluation. These active compounds exhibited broad spectrum of various biological activities. Most of the compounds showed potent activity.

scholarly journals Preparation, characterization and featuring of an inclusion complex of nerol with β-cyclodextrin

2017 ◽  
Vol 5 (2) ◽  
pp. 195
Author(s):  
Mayara Coêlho ◽  
Herlane Da Silva ◽  
Muhammad Islam ◽  
Vicente Viana ◽  
Ana Amélia Melo-Cavalcante
Keyword(s):  
Inclusion Complex ◽  
Inclusion Complexes ◽  
Biological Activities ◽  
Aqueous Media ◽  
Limiting Factor ◽  
Thermo Gravimetric ◽  
Drug Molecules ◽  
Complex Cavity ◽  
Nonpolar Molecules ◽  
Low Solubility

Nerol is an acyclic type monoterpene with important biological activities. However, the low solubility in aqueous media is a limiting factor for its user. Cyclodextrins have been widely used in order to improve the solubility, stability and bioavailability of nonpolar molecules through the formation of inclusion complexes. Thus, the present study consists in the development of nerol inclusion complex in combination with the β-cyclodextrin (β-CD) followed by characterizing by thermal analysis and spectrophotometric absorption in the infrared (FTIR). The results suggest a complexation of nerol with β-CD having detours and changed the intensity of various bands. The thermo gravimetric curve of CI found to indicate an output of solvating water molecules from the complex cavity formed for replacement of drug molecules probably included. Thus, it is concluded a possibility to obtain inclusion complexes of nerol monoterpene with β-CD, which will increase its solubility and facilitate delivery process.

scholarly journals Activity-relevant similarity values for fingerprints and implications for similarity searching

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 591 ◽  
Author(s):  
Swarit Jasial ◽  
Ye Hu ◽  
Martin Vogt ◽  
Jürgen Bajorath
Keyword(s):  
Characteristic Feature ◽  
Success Rate ◽  
Similarity Search ◽  
Unsolved Problem ◽  
Biological Activities ◽  
Similarity Searching ◽  
Search Performance ◽  
General Activity ◽  
Active Compounds ◽  
Scientific Foundation

A largely unsolved problem in chemoinformatics is the issue of how calculated compound similarity relates to activity similarity, which is central to many applications. In general, activity relationships are predicted from calculated similarity values. However, there is no solid scientific foundation to bridge between calculated molecular and observed activity similarity. Accordingly, the success rate of identifying new active compounds by similarity searching is limited. Although various attempts have been made to establish relationships between calculated fingerprint similarity values and biological activities, none of these has yielded generally applicable rules for similarity searching. In this study, we have addressed the question of molecular versus activity similarity in a more fundamental way. First, we have evaluated if activity-relevant similarity value ranges could in principle be identified for standard fingerprints and distinguished from similarity resulting from random compound comparisons. Then, we have analyzed if activity-relevant similarity values could be used to guide typical similarity search calculations aiming to identify active compounds in databases. It was found that activity-relevant similarity values can be identified as a characteristic feature of fingerprints. However, it was also shown that such values cannot be reliably used as thresholds for practical similarity search calculations. In addition, the analysis presented herein helped to rationalize differences in fingerprint search performance.

scholarly journals DeltaDelta Neural Networks for Lead Optimization of Small Molecule Potency

2019 ◽  
Author(s):  
Jose Jimenez-Luna ◽  
Laura Pérez-Benito ◽  
Gerard Martinez-Rosell ◽  
Simone Sciabola ◽  
Rubben Torella ◽  
...  
Keyword(s):  
Neural Networks ◽  
Lead Optimization ◽  
Learning Approach ◽  
Potential Drug ◽  
Protein Target ◽  
Drug Molecules ◽  
Simulation Based ◽  
Machine Learning Approach ◽  
Fundamental Challenge ◽  
Deep Learning Model

The capability to rank different potential drug molecules against a protein target for potency has always been a fundamental challenge in computational chemistry due to its importance in drug design. While several simulation-based methodologies exist, they are hard to use prospectively and thus predicting potency in lead optimization campaigns remains an open challenge. Here we present the first machine learning approach specifically tailored for ranking ranking congeneric series based on deep 3D-convolutional neural networks. Furthermore we prove its effectiveness by blindly testing it on datasets provided by Janssen, Pfizer and Biogen totalling over 3246 ligands and 13 targets as well as several well-known openly available sets, representing one the largest evaluations ever performed. We also performed online learning simulations of lead optimization using the approach in a predictive manner obtaining significant advantage over experimental choice. We believe that the evaluation performed in this study is strong evidence of the usefulness of a modern deep learning model in lead optimization pipelines against more expensive simulation-based alternatives.

scholarly journals Co-Microencapsulation of Anthocyanins from Black Currant Extract and Lactic Acid Bacteria in Biopolymeric Matrices

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1700 ◽  
Author(s):  
Iuliana Maria Enache ◽  
Aida Mihaela Vasile ◽  
Elena Enachi ◽  
Vasilica Barbu ◽  
Nicoleta Stănciuc ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Biological Activities ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Confocal Laser ◽  
In Vitro Digestibility ◽  
Black Currant ◽  
Active Compounds ◽  
Food Ingredients

Anthocyanins from black currant extract and lactic acid bacteria were co-microencapsulated using a gastro-intestinal-resistant biocomposite of whey protein isolate, inulin, and chitosan, with an encapsulation efficiency of 95.46% ± 1.30% and 87.38% ± 0.48%, respectively. The applied freeze-drying allowed a dark purple stable powder to be obtained, with a satisfactory content of phytochemicals and 11 log colony forming units (CFU)/g dry weight of powder (DW). Confocal laser microscopy displayed a complex system, with several large formations and smaller aggregates inside, consisting of biologically active compounds, lactic acid bacteria cells, and biopolymers. The powder showed good storage stability, with no significant changes in phytochemicals and viable cells over 3 months. An antioxidant activity of 63.64 ± 0.75 mMol Trolox/g DW and an inhibitory effect on α-amylase and α-glucosidase of 87.10% ± 2.08% and 36.96% ± 3.98%, respectively, highlighted the potential biological activities of the co-microencapsulated powder. Significantly, the in vitro digestibility profile showed remarkable protection in the gastric environment, with controlled release in the intestinal simulated environment. The powder was tested by addition into a complex food matrix (yogurt), and the results showed satisfactory stability of biologically active compounds when stored for 21 d at 4 °C. The obtained results confirm the important role of microencapsulation in ensuring a high degree of protection, thus allowing new approaches in developing food ingredients and nutraceuticals, with enhanced functionalities.

scholarly journals Recent Advances in Indazole-Containing Derivatives: Synthesis and Biological Perspectives

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2783 ◽  
Author(s):  
Shu-Guang Zhang ◽  
Chao-Gen Liang ◽  
Wei-Hua Zhang
Keyword(s):  
Functional Groups ◽  
Medicinal Chemistry ◽  
Biological Activities ◽  
Drug Molecules ◽  
Recent Advances

Indazole-containing derivatives represent one of the most important heterocycles in drug molecules. Diversely substituted indazole derivatives bear a variety of functional groups and display versatile biological activities; hence, they have gained considerable attention in the field of medicinal chemistry. This review aims to summarize the recent advances in various methods for the synthesis of indazole derivatives. The current developments in the biological activities of indazole-based compounds are also presented.

Carrageenan: A Wonder Polymer from Marine Algae for Potential Drug Delivery Applications

2019 ◽  
Vol 25 (11) ◽  
pp. 1172-1186 ◽  
Author(s):  
Dilshad Qureshi ◽  
Suraj Kumar Nayak ◽  
Samarendra Maji ◽  
Doman Kim ◽  
Indranil Banerjee ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Biological Activities ◽  
Medical Science ◽  
Drug Carriers ◽  
Sulfated Polysaccharides ◽  
Potential Drug ◽  
Natural Polymers ◽  
Structural Variations ◽  
Varied Range ◽  
Drug Delivery Applications

Background: With the advancement in the field of medical science, the idea of sustained release of the therapeutic agents in the patient’s body has remained a major thrust for developing advanced drug delivery systems (DDSs). The critical requirement for fabricating these DDSs is to facilitate the delivery of their cargos in a spatio-temporal and pharmacokinetically-controlled manner. Albeit the synthetic polymer-based DDSs normally address the above-mentioned conditions, their potential cytotoxicity and high cost have ultimately constrained their success. Consequently, the utilization of natural polymers for the fabrication of tunable DDSs owing to their biocompatible, biodegradable, and non-toxic nature can be regarded as a significant stride in the field of drug delivery. Marine environment serves as an untapped resource of varied range of materials such as polysaccharides, which can easily be utilized for developing various DDSs. Methods: Carrageenans are the sulfated polysaccharides that are extracted from the cell wall of red seaweeds. They exhibit an assimilation of various biological activities such as anti-thrombotic, anti-viral, anticancer, and immunomodulatory properties. The main aim of the presented review is threefold. The first one is to describe the unique physicochemical properties and structural composition of different types of carrageenans. The second is to illustrate the preparation methods of the different carrageenan-based macro- and micro-dimensional DDSs like hydrogels, microparticles, and microspheres respectively. Fabrication techniques of some advanced DDSs such as floating hydrogels, aerogels, and 3-D printed hydrogels have also been discussed in this review. Next, considerable attention has been paid to list down the recent applications of carrageenan-based polymeric architectures in the field of drug delivery. Results: Presence of structural variations among the different carrageenan types helps in regulating their temperature and ion-dependent sol-to-gel transition behavior. The constraint of low mechanical strength of reversible gels can be easily eradicated using chemical crosslinking techniques. Carrageenan based-microdimesional DDSs (e.g. microspheres, microparticles) can be utilized for easy and controlled drug administration. Moreover, carrageenans can be fabricated as 3-D printed hydrogels, floating hydrogels, and aerogels for controlled drug delivery applications. Conclusion: In order to address the problems associated with many of the available DDSs, carrageenans are establishing their worth recently as potential drug carriers owing to their varied range of properties. Different architectures of carrageenans are currently being explored as advanced DDSs. In the near future, translation of carrageenan-based advanced DDSs in the clinical applications seems inevitable.

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