scholarly journals Structure-Activity Studies of Melatonin Analogues in Prepubertal Male Rats

1988 ◽  
Vol 41 (3) ◽  
pp. 393 ◽  
Author(s):  
DJ Kennaway ◽  
HM Hugel ◽  
S Clarke ◽  
A Tjandra ◽  
D WJohnson ◽  
...  
Keyword(s):  
Biological Activity ◽  
Rat Model ◽  
Sexual Development ◽  
Biologically Active ◽  
Male Rats ◽  
Side Chain ◽  
Structure Activity ◽  
Metabolic Products ◽  
Biological Potency ◽  
Melatonin Analogues

Comparison has been made between the activity of the pineal hormone melatonin, and several analogues and metabolites in inhibiting sexual development in a protein-restricted prepubertal rat model. Eleven melatonin analogues or metabolites were tested with the aim of evaluating the model as a test of the hypothesis that melatonin acts as a prohormone and that the ring schism metabolites (kynurenamines) mediate many of the effects attributable to melatonin. Although the hypothesis could not be confirmed, modification of the melatonin structure by lengthening the acylamide side chain or by replacing the 5 methoxy function with fluorine resulted in loss of biological potency. Modification of the melatonin structure to block the two known points of metabolism resulted in no significant alteration in biological activity. Thus 6-chloromelatonin (blocking 6-hydroxylation) and 2,3-dihydromelatonin (blocking oxidative cleavage of the C2-C3 bond) and 6-chloro-2,3-dihydromelatonin remained biologically active. The metabolic products of brain indolearnine-2,3-dioxygenase, N-acetyl-N2-formyl-5-methoxy kynurenamine (aFoMK) and N-acetyl-5-methoxy kynurenamine (aMK), paradoxically were also biologically active.

Analogues of the cholecystokinin octapeptide modified in the central part of the molecule

1991 ◽  
Vol 56 (9) ◽  
pp. 1963-1970 ◽  
Author(s):  
Jan Hlaváček ◽  
Václav Čeřovský ◽  
Jana Pírková ◽  
Pavel Majer ◽  
Lenka Maletínská ◽  
...  
Keyword(s):  
Amino Acid ◽  
Biological Activities ◽  
Point Of View ◽  
Biologically Active ◽  
Side Chain ◽  
Amino Acid Residues ◽  
Cholecystokinin Octapeptide ◽  
Biological Tests ◽  
Biological Potency ◽  
Biologically Active Conformation

In a series of analogues of the cholecystokinin octapeptide (CCK-8) the amino acid residues were gradually modified by substituting Gly by Pro in position 4, Trp by His in position 5, Met by Cle in position 6, or the Gly residue was inserted between Tyr and Met in positions 2 and 3 of the peptide chain, and in the case of the cholecystokinin heptapeptide (CCK-7) the Met residues were substituted by Nle or Aib. These peptides were investigated from the point of view of their biological potency in the peripheral and central region. From the results of the biological tests it follows that the modifications carried out in these analogues and in their Nα-Boc derivatives mean a suppression of the investigated biological activities by 2-3 orders of magnitude (at a maximum dose of the tested substance of 2 . 10-2 mg per animal).This means that a disturbance of the assumed biologically active conformation of CCK-8, connected with a considerable decrease of the biological potency of the molecule, takes place not only after introduction of the side chain into its centre (substitution of Gly4), but also after the modification of the side chains of the amino acids or by extension of the backbone in further positions around this central amino acid.

Biologically active compounds from bryophytes

2007 ◽  
Vol 79 (4) ◽  
pp. 557-580 ◽  
Author(s):  
Yoshinori Asakawa
Keyword(s):  
Biological Activity ◽  
Aromatic Compounds ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Active Compounds ◽  
Lead Compounds ◽  
Structure Activity ◽  
Medicinal Properties

Liverworts produce a great variety of lipophilic terpenoids, aromatic compounds, and acetogenins. Many of these constituents have characteristic scents, pungency, and bitterness, and display a quite extraordinary array of bioactivities and medicinal properties. These expressions of biological activity are summarized and discussed, and examples are given of the potential of certain lead compounds for structure-activity studies and synthesis.

scholarly journals Identifying Structural Features of Sulforaphane Derivatives Based on QM Force Field for Predicting the Anti-Cancer Activity

2020 ◽  
Vol 8 (6) ◽  
pp. 1631-1636
Keyword(s):  
Biological Activity ◽  
Cancer Cells ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Structural Features ◽  
Biologically Active ◽  
Structure Activity ◽  
Anti Cancer ◽  
Derivatives Of ◽  
Cancer Activity

Sulforaphane (SFN) is a biologically active compound-based drug obtained from cruciferous vegetables, which has been investigated for its anti-tumor and chemopreventive effects. SFN shows a potential mechanism of its anti-cancer activity by binding to Macrophage Migration Inhibitory Factor (MIF) which is a pleiotropic cytokine that overexpresses in cancer cells increasing the aggressiveness of the disease. SFN can significantly inhibit the action of MIF on angiogenesis and the prevention of apoptosis in cancer cells. Preclinical studies on the anti-cancer activity of SFN showed promising results but in clinical studies, it is not yet convincing. Screening of a set of compounds chemically related to SFN can have a chance of showing promising anticancer activity. The quantitative structure activity relationship (QSAR) based on quantum mechanics has been done to derive the best mathematical model of these selected derivatives of sulforaphane for the calculation of its biological activity. These sulforaphane derivatives have been evaluated with respect to their ADMET and physicochemical properties. Validation was done to indicate the predictiveness of the model. The significant R2 value of 0.5676 between experimental and predicted biological activity and R2 cv value of 0.554 depicts a decent statistical fit of the model. A best QSAR model has been selected which has a future scope of helping in designing anti-cancerous drugs.

Biological Activity of Trans-Membrane Anion Carriers

2018 ◽  
Vol 25 (30) ◽  
pp. 3560-3576 ◽  
Author(s):  
Massimo Tosolini ◽  
Paolo Pengo ◽  
Paolo Tecilla
Keyword(s):  
Biological Activity ◽  
Membrane Transport ◽  
Anticancer Agents ◽  
Biological Effects ◽  
Structure Activity Relationship ◽  
New Drugs ◽  
Activity Relationship ◽  
Anion Channels ◽  
Cellular Homeostasis ◽  
Structure Activity

Natural and synthetic anionophores promote the trans-membrane transport of anions such as chloride and bicarbonate. This process may alter cellular homeostasis with possible effects on internal ions concentration and pH levels triggering several and diverse biological effects. In this article, an overview of the recent results on the study of aniontransporters, mainly acting with a carrier-type mechanism, is given with emphasis on the structure/activity relationship and on their biological activity as antibiotic and anticancer agents and in the development of new drugs for treating conditions derived from dysregulation of natural anion channels.

Neurotoxicity of Pesticides: The Roadmap for the Cubic Mode of Action

2020 ◽  
Vol 27 (1) ◽  
pp. 54-77 ◽  
Author(s):  
Bogdan Bumbăcilă ◽  
Mihai V. Putz
Keyword(s):  
Biological Activity ◽  
Wiener Index ◽  
Laboratory Animals ◽  
Covalent Bonds ◽  
Organophosphate Compounds ◽  
Sar Studies ◽  
Structure Activity ◽  
Cubic Structure

Pesticides are used today on a planetary-wide scale. The rising need for substances with this biological activity due to an increasing consumption of agricultural and animal products and to the development of urban areas makes the chemical industry to constantly investigate new molecules or to improve the physicochemical characteristics, increase the biological activities and improve the toxicity profiles of the already known ones. Molecular databases are increasingly accessible for in vitro and in vivo bioavailability studies. In this context, structure-activity studies, by their in silico - in cerebro methods, are used to precede in vitro and in vivo studies in plants and experimental animals because they can indicate trends by statistical methods or biological activity models expressed as mathematical equations or graphical correlations, so a direction of study can be developed or another can be abandoned, saving financial resources, time and laboratory animals. Following this line of research the present paper reviews the Structure-Activity Relationship (SAR) studies and proposes a correlation between a topological connectivity index and the biological activity or toxicity made as a result of a study performed on 11 molecules of organophosphate compounds, randomly chosen, with a basic structure including a Phosphorus atom double bounded to an Oxygen atom or to a Sulfur one and having three other simple covalent bonds with two alkoxy (-methoxy or -ethoxy) groups and to another functional group different from the alkoxy groups. The molecules were packed on a cubic structure consisting of three adjacent cubes, respecting a principle of topological efficiency, that of occupying a minimal space in that cubic structure, a method that was called the Clef Method. The central topological index selected for correlation was the Wiener index, since it was possible this way to discuss different adjacencies between the nodes in the graphs corresponding to the organophosphate compounds molecules packed on the cubic structure; accordingly, "three dimensional" variants of these connectivity indices could be considered and further used for studying the qualitative-quantitative relationships for the specific molecule-enzyme interaction complexes, including correlation between the Wiener weights (nodal specific contributions to the total Wiener index of the molecular graph) and the biochemical reactivity of some of the atoms. Finally, when passing from SAR to Q(uantitative)-SAR studies, especially by the present advanced method of the cubic molecule (Clef Method) and its good assessment of the (neuro)toxicity of the studied molecules and of their inhibitory effect on the target enzyme - acetylcholinesterase, it can be seen that a predictability of the toxicity and activity of different analogue compounds can be ensured, facilitating the in vivo experiments or improving the usage of pesticides.

Studies on the EC50 of Natural Monoterpenes as Fungal Inhibitors with Quantitative Structure-Activity Relationships (QSARs)

2020 ◽  
Vol 10 (1) ◽  
pp. 44-60
Author(s):  
Mohamed E.I. Badawy ◽  
Entsar I. Rabea ◽  
Samir A.M. Abdelgaleil
Keyword(s):  
Biological Activity ◽  
Plant Pathogens ◽  
Molecular Descriptors ◽  
Microbial Pathogens ◽  
Quantitative Structure ◽  
Qsar Study ◽  
Qsar Analysis ◽  
Pharmacophore Modelling ◽  
Structure Activity ◽  
Wide Range

Background:Monoterpenes are the main constituents of the essential oils obtained from plants. These natural products offered wide spectra of biological activity and extensively tested against microbial pathogens and other agricultural pests.Methods:Antifungal activity of 10 monoterpenes, including two hydrocarbons (camphene and (S)- limonene) and eight oxygenated hydrocarbons ((R)-camphor, (R)-carvone, (S)-fenchone, geraniol, (R)-linalool, (+)-menthol, menthone, and thymol), was determined against fungi of Alternaria alternata, Botrytis cinerea, Botryodiplodia theobromae, Fusarium graminearum, Phoma exigua, Phytophthora infestans, and Sclerotinia sclerotiorum by the mycelia radial growth technique. Subsequently, Quantitative Structure-Activity Relationship (QSAR) analysis using different molecular descriptors with multiple regression analysis based on systematic search and LOOCV technique was performed. Moreover, pharmacophore modelling was carried out using LigandScout software to evaluate the common features essential for the activity and the hypothetical geometries adopted by these ligands in their most active forms.Results:The results showed that the antifungal activities were high, but depended on the chemical structure and the type of microorganism. Thymol showed the highest effect against all fungi tested with respective EC50 in the range of 10-86 mg/L. The QSAR study proved that the molecular descriptors HBA, MR, Pz, tPSA, and Vp were correlated positively with the biological activity in all of the best models with a correlation coefficient (r) ≥ 0.98 and cross-validated values (Q2) ≥ 0.77.Conclusion:The results of this work offer the opportunity to choose monoterpenes with preferential antimicrobial activity against a wide range of plant pathogens.

scholarly journals Synthesis and Biological Activity of Brassinosteroid Analogues with a Nitrogen-Containing Side Chain

2020 ◽  
Vol 22 (1) ◽  
pp. 155
Author(s):  
Mikhail V. Diachkov ◽  
Karoll Ferrer ◽  
Jana Oklestkova ◽  
Lucie Rarova ◽  
Vaclav Bazgier ◽  
...  
Keyword(s):  
Biological Activity ◽  
Functional Groups ◽  
Side Chain ◽  
Biotic And Abiotic Stresses ◽  
Short Side ◽  
Arabidopsis Root ◽  
Physiological Processes ◽  
Growth Promoting ◽  
The Impact ◽  
Brassinosteroid Analogues

Brassinosteroids are a class of plant hormones that regulate a broad range of physiological processes such as plant growth, development and immunity, including the suppression of biotic and abiotic stresses. In this paper, we report the synthesis of new brassinosteroid analogues with a nitrogen-containing side chain and their biological activity on Arabidopis thaliana. Based on molecular docking experiments, two groups of brassinosteroid analogues were prepared with short and long side chains in order to study the impact of side chain length on plants. The derivatives with a short side chain were prepared with amide, amine and ammonium functional groups. The derivatives with a long side chain were synthesized using amide and ammonium functional groups. A total of 25 new brassinosteroid analogues were prepared. All 25 compounds were tested in an Arabidopsis root sensitivity bioassay and cytotoxicity screening. The synthesized substances showed no significant inhibitory activity compared to natural 24-epibrassinolide. In contrast, in low concentration, several compounds (8a, 8b, 8e, 16e, 22a and 22e) showed interesting growth-promoting activity. The cytotoxicity assay showed no toxicity of the prepared compounds on cancer and normal cell lines.

scholarly journals Relationship of 25-hydroxyvitamin D3 side chain structure to biological activity.

1975 ◽  
Vol 250 (1) ◽  
pp. 226-230
Author(s):  
M F Holick ◽  
M Garabedian ◽  
H K Schnoes ◽  
H F DeLuca
Keyword(s):  
Biological Activity ◽  
Chain Structure ◽  
Side Chain ◽  
Relationship Of

scholarly journals Hydrazones of 4-(Trifluoromethyl)benzohydrazide as New Inhibitors of Acetyl- and Butyrylcholinesterase

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 989
Author(s):  
Martin Krátký ◽  
Katarína Svrčková ◽  
Quynh Anh Vu ◽  
Šárka Štěpánková ◽  
Jarmila Vinšová
Keyword(s):  
Biological Activity ◽  
Mixed Type ◽  
Cholinesterase Inhibitors ◽  
Eukaryotic Cell ◽  
Structure Activity ◽  
Aliphatic Ketones ◽  
Ic50 Values ◽  
Central Nervous Systems ◽  
Dual Inhibition ◽  
Potential Inhibitors

Based on the broad spectrum of biological activity of hydrazide–hydrazones, trifluoromethyl compounds, and clinical usage of cholinesterase inhibitors, we investigated hydrazones obtained from 4-(trifluoromethyl)benzohydrazide and various benzaldehydes or aliphatic ketones as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). They were evaluated using Ellman’s spectrophotometric method. The hydrazide–hydrazones produced a dual inhibition of both cholinesterase enzymes with IC50 values of 46.8–137.7 µM and 19.1–881.1 µM for AChE and BuChE, respectively. The majority of the compounds were stronger inhibitors of AChE; four of them (2-bromobenzaldehyde, 3-(trifluoromethyl)benzaldehyde, cyclohexanone, and camphor-based 2o, 2p, 3c, and 3d, respectively) produced a balanced inhibition of the enzymes and only 2-chloro/trifluoromethyl benzylidene derivatives 2d and 2q were found to be more potent inhibitors of BuChE. 4-(Trifluoromethyl)-N’-[4-(trifluoromethyl)benzylidene]benzohydrazide 2l produced the strongest inhibition of AChE via mixed-type inhibition determined experimentally. Structure–activity relationships were identified. The compounds fit physicochemical space for targeting central nervous systems with no apparent cytotoxicity for eukaryotic cell line together. The study provides new insights into this CF3-hydrazide–hydrazone scaffold.

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