Natural ten-membered lactones: sources, structural diversity, biological activity, and intriguing future.

An attempt was made to construct an adequate model of interrelation of radioprotective properties of biologically active chemical compounds with their electronic and information factors. Biological activity (radiation protective effects) of chemical compounds has been analyzed in relation to their electronic sign and the information function. Statistical comparison of qualitative indices has revealed that electronic and information signs the most informative characteristics of the molecules responsible for radiation protective action. Correlation equations are given for electronic and information dependent change in the antiradiation properties of the molecule. Quantitative estimates were made associating the protective efficiency of the chemical compounds under study with variations in the electronic parameters and dose of chemicals.

The main objective of this study was to evaluate the biological activity of a new compound (derived from aza-bicyclo-carboxylic acid) against heart failure caused by the ischemia- reperfusion phenomenon. In addition, to characterize de molecular mechanism involved in the effect exerted by aza-bicyclo-carboxylic acid against infarction area, some drugs such as prazosin, metoprolol, propanolol, tamoxifen, flutamide, finasteride, nifedipine, levosimedan, adenosine, rolofylline, isoproterenol and the compound ZM-241385 were used as pharmacological tools. The data found indicated that biological activity induced by compound 3 on infarction area only was similar at effect exerted by adenosine; however, the effect produced by compound 3 was blocked with of rolofylline. Other data showed that the biological activity of compound 3 decreases the cAMP levels in a time-dependent manner. In conclusion, the results indicate that compound 3 can produce a cardioprotective effect against myocardial ischemia-reperfusion injury translated as a decrease on infarction area; this phenomenon involves A1-adenosine receptor activation and, as a result may cause changes in cAMP levels.

The literature data and the results of our own investigations on the comparative study of the biological activity of isostructural organogermanium and organosilicon compounds have been summarized. It has been shown that the series of organogermanium and organosilicon compounds is more active than the carbon analogues, the majority of organogermanium compounds are less toxic than the sila analogues, the biological activity of the compounds under study appears to be similar but can dramatically differ in the degree of activity, and, moreover, in some particular cases sila and germa analogues exhibit the opposite biological effects.

The biologically active compounds derived from different natural organisms such as animals, plants, and microorganisms like algae, fungi, bacteria and merine organisms. These natural compounds possess diverse biological activities like anthelmintic, antibacterial, antifungal, antimalarial, antiprotozoal, antituberculosis, and antiviral activities. These biological active compounds were acted by variety of molecular targets and thus may potentially contribute to several pharmacological classes. The synthesis of natural products and their analogues provides effect of structural modifications on the parent compounds which may be useful in the discovery of potential new drug molecules with different biological activities. Natural organisms have developed complex chemical defense systems by repelling or killing predators, such as insects, microorganisms, animals etc. These defense systems have the ability to produce large numbers of diverse compounds which can be used as new drugs. Thus, research on natural products for novel therapeutic agents with broad spectrum activities and will continue to provide important new drug molecules.

Synthesis, characterization, and biological activities of novel organometallic compounds of rhenium(I) with 2-(2-benzylidenehydrazinyl) benzothiazole Schiff-base derivatives: Molecular docking, ADME, and DFT studies.

2,4,5-Tris(alkoxyaryl)imidazoline derivatives as potent scaffold for novel p53-MDM2 interaction inhibitors: Design, synthesis, and biological evaluation.

A structure-activity relationship study (SAR) was applied to correlate the biological activities of m-alkoxyphenol compounds on Chromobacterium violaceum respiration with chemical structure properties. The biological activities of these compounds on metabolism rates were obtained through microcalorimetry. The calculations to estimate several physicochemical properties were carried out at the semi-empirical AM1 and ab initio DFT levels using the CEP-31G basis set and were parameterized using the continuum-solvation model COSMO for solvent contribution. m-alkoxyphenols properties were evaluated by chemometric analyses to carry out a correlation between the physicochemical properties and their biological effects. These compound effects increase with lateral hydrocarbon chain length, volume, dipole moment, proton affinity, energies of HOMO and LUMO, partition coefficient and enthalpy of formation and decrease with solvent effects and ionization enthalpy.

The microcomputer OASIS system for predicting the biological activity of chemical compounds

Traditional Chinese Medicine (TCM) is a valuable source of chemical and structural diversity discovery, who has thousands of years of history. In long-term clinical practice, it generated more than 1,000 commonly used TCMs and prescriptions with exact curative effects and high safety. Researchers have made many efforts over the past few decades, from finding a single active compound to identifying a combination of compounds. The successful discovery of artemisinin and salvia are good samples. Fragment-based drug discovery is a method to design and establish a compound library composed of fragments, and to screen the compounds for biological activity. The X-ray crystallography, nuclear magnetic resonance and mass spectrometry were used to analyse the binding mode and binding strength of these fragments and target proteins, and based on the structural information, the structure of the fragment molecules was optimised to obtain lead compounds. Owing to the success of TCM in the drug discovery area, the main aim of this project was to chemically investigate the small molecules produced by the selected TCM—Ligusticum Chuanxiong. This project is part of an effort to modernise TCM and will involve assessing low Molecular Weight TCM constituents by the relatively new Fragment-Based Drug Discovery technique. Two libraries, a fragment library isolated from Chuanxiong and a virtual fragment library from the Literature were constructed and their chemical diversity were evaluated by self-organizing map (SOM). In this study, we have also used Magnetic Resonance Mass Spectrometry (MRMS) to perform a targeted screening of the constructed TCM fragment library against three tuberculosis proteins. This project presents efforts to achieve an effective approach to discover TCM by analysis two kinds of libraries based on Fragment-Based Drug Discovery (FBDD). The first chapter introduced the history and development of TCM, FBDD theory for building a library. Based on these backgrounds, the idea of building a TCM based FBDD library was generated. It also covers a review on structure diversity analysis and target identification, which used as the approaches to evaluate the libraries. The results are presented in chapters 2 to 4. Chapter 2 presents the whole process of extraction and isolation of a TCM Chuanxiong by different chromatographic methods. Structures of the isolated compounds were determined by NMR and MS data. A fragment library of eight compounds as well as a “peak” library, were obtained and analysed. Chapter 3 describes the diversity analysis of the virtual Chuanxiong fragment library using self-organizing map (SOM). The library consists of 122 reported low molecular weight (MW) compounds. With the aim to test the diversity of this library, eight 25*25 sized SOMs and four 10*10 sized SOMs were generated against an existed natural product library containing 20,185 low MW compounds. Chapter 4 presents the FTMS analysis for 3 tuberculosis (TB) proteins. The “peak” library in chapter 2 was screened against the 3 TB proteins. Unfortunately, no protein-ligand complex was observed. The thesis is a brief process for TCM based FBDD research. For valuable TCM, it is able to isolate and generate libraries, which represent a large chemical space for target identification. It can be used for future drug discovery.

Biologically active compounds (BAC) of plants are represented by various classes of organic compounds and are a prospective raw material for developing therapeutic and preventive remedies. There are more than 6,000 plant species on the territory of the Republic of Kazakhstan that might become a source of raw materials for development and production of new domestic original phyto-pharmaceuticals. Therefore, testing of biologically active compounds extracted from Kazakhstan’s wild-growing plants is a timely and promising task. It was determined that the roots of two wild plants of Kazakhstan flora - Salvia deserta and Vexibia alopecuroides contain biologically active compounds with high a) antibacterial and antifungicidal activities estimated by the IC50 index, b) anti-inflammatory activity estimated by the ability to inhibit production of nitric oxide, c) therapeutically significant antioxidant potential with respect to the ABTS.+ radical cations. Crude extracts of biologically active compounds from the roots of S. deserta and V. alopecuroides plants that have the above mentioned activities were obtained by maceration with methylene chloride, purified into individual compounds using flash and gas chromatography. It was determined that 9 individual compounds that revealed biological activity were isolated from Vexibia alopecuroides roots’ extract, which belongs to flavonoids, and 4 compounds were isolated from Salvia deserta roots’ extract, which belongs to diterpenoids. Individual compounds isolated from Salvia deserta and Vexibia alopecuroides roots’ extract showed antimicrobial activity against S. aureus, Methicillin-resistant S. aureus, P. aeruginosa, C. glabrata, C. krusei, C. albicans with an IC50 index within the range of < 0, 8 to 13.38 μg / ml. It allows to consider them as potential candidates for development of new-galenic phyto-pharmaceuticals. Key words: biologically active compounds, crude extracts, antimicrobial activity, Salvia deserta, Vexibia alopecuroides.

This study aimed to quantify the active biological compounds in Origanum vulgare subsp.glandulosum Desf. Analysis of the chemical composition essential oil from Tunisia was carried out using gas chromatography-mass spectral (GC-MS). The antioxidant capacities of essential oil and extracts were evaluated using free radical scavenging, ferric reducing antioxidant power assay and metal chelating effects. The antidiabetic activity was screened using α-amylase. The oil was dominated by carvacrol (61.20 to 74.03), p-cymene (5.89 to 12.60), and g-terpinene (1.13 to 6.88). 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant power assay (FRAP) assays showed that leaves of O. vulgare have a potent antioxidant activities which was comparable to Trolox. The methanol extract have the highest ion chelating ability at around 76.98 mg equivalent ethylenediaminetetraacetic acid (EDTA)/g dry matter (DM). The amounts of chlorophylls A and B were higher than that of lycopene and β-carotene. Essential oils and extracts, screened for α-amylase inhibitory effect, showed a strong capacity to inhibit the degradation of starch by pancreatic and salivary α-amylase. Extracts and essential oils of O. vulgare showed substantial antioxidant activity, and detectible inhibitory effect on α-amylase activity, therefore it could be used as a natural preservative ingredient in food and/or pharmaceutical industries. Key words: Origanum vulgare subsp. glandulosum, essential oil, solvent extract, biological activities.

Chapter 12 - New hybrid materials for wound cover dressings

A lot of high quality data on the biological activity of chemical compounds are required throughout the whole drug discovery process: from development of computational models of the structure-activity relationship to experimental testing of lead compounds and their validation in clinics. Currently, a large amount of such data is available from databases, scientific publications, and patents. Biological data are characterized by incompleteness, uncertainty, and low reproducibility. Despite the existence of free and commercially available databases of biological activities of compounds, they usually lack unambiguous information about peculiarities of biological assays. On the other hand, scientific papers are the primary source of new data disclosed to the scientific community for the first time. In this study, we have developed and validated a data-mining approach for extraction of text fragments containing description of bioassays. We have used this approach to evaluate compounds and their biological activity reported in scientific publications. We have found that categorization of papers into relevant and irrelevant may be performed based on the machine-learning analysis of the abstracts. Text fragments extracted from the full texts of publications allow their further partitioning into several classes according to the peculiarities of bioassays. We demonstrate the applicability of our approach to the comparison of the endpoint values of biological activity and cytotoxicity of reference compounds.

Natural products from plants have the potential to exert antioxidant, anti-tyrosinase, antibacterial, and cytotoxic activities and have been widely used as ingredients in cosmetics, medicines, or supplementary food. Several types of secondary metabolites from the Citrus genus have been reported to exhibit interesting biological activity. Due to this lack of studies and biological activity of compounds from related species, it was considered important to investigate Citrus grandis Linn. (Tubtim Siam Pomelo) to be studied. The objective of this research was to isolate and elucidate the structures of chemical constituents and to evaluate their biological activity from the peels of C. grandis Linn. A coumarin (1) and 3 flavonoids (2 - 4) were isolated from the peels of C. grandis Linn. The structures of these compounds were elucidated by analyses of spectroscopic data as well as comparison of their spectroscopic data with the previously published data. Compounds 1 - 4 have been evaluated for antioxidant, anti-tyrosinase, antibacterial and cytotoxic activities. Compound 2 showed the highest inhibition in DPPH and tyrosinase with IC50 values of 0.219 ± 0.011 and 0.033 ± 0.002 mg/mL, respectively. Interestingly, compound 1 - 4 were the first time being isolated from Tubtim Siam Pomelo. HIGHLIGHTS Chemical constituents from grandis Linn. (Tubtim Siam Pomelo) have not been reported Coumarin and flavonoids have been isolated from acetone extract (-) meranzin hydrate, 5-demethoxynobiletin, tangeretin and naringin were isolated for the first time from Tubtim Siam Pomelo Four compounds exhibited good antioxidant and anti-tyrosinase activities GRAPHICAL ABSTRACT

The prediction of the biological activity of chemical compounds by means of mathematical models is discussed. Biological activity of chemicals, including their toxicity on man and other biological organisms and systems, involves too complex phenomena to presently be predictable by fundamental models such as ab initio quantum mechanical models or statistical mechanical models. Hence one takes recourse to semi-empirical and empirical models which relate the variation in chemical structure of chemical compounds to the variation in their measured biological activity, e.g. toxicity in one or several test systems. These models are "calibrated" on series of similar compounds with "known" toxicity, the training set. Thereafter the models can--in fortunate cases--be used to predict the toxicity of compounds which are structurally similar to the training set compounds. The formulation and applicability of semi-empirical and empirical models relating chemical structure to biological activity is discussed. Causes and remedies for commonly encountered fallacies are presented.