scholarly journals Synthesis of C2-Alkoxy-Substituted 19-Nor Vitamin D3 Derivatives: Stereoselectivity and Biological Activity

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 69
Author(s):  
Yuka Mizumoto ◽  
Ryota Sakamoto ◽  
Akiko Nagata ◽  
Suzuka Sakane ◽  
Atsushi Kittaka ◽  
...  
Keyword(s):  
Biological Activity ◽  
Side Effects ◽  
Vitamin D3 ◽  
Biological Activities ◽  
Active Form ◽  
Coupling Reaction ◽  
Sar Studies ◽  
Structure Activity ◽  
Type Coupling ◽  
Alkoxy Groups

The active form of vitamin D3 (D3), 1a,25-dihydroxyvitamn D3 (1,25D3), plays a central role in calcium and bone metabolism. Many structure–activity relationship (SAR) studies of D3 have been conducted, with the aim of separating the biological activities of 1,25D3 or reducing its side effects, such as hypercalcemia, and SAR studies have shown that the hypercalcemic activity of C2-substituted derivatives and 19-nor type derivatives is significantly suppressed. In the present paper, we describe the synthesis of 19-nor type 1,25D3 derivatives with alkoxy groups at C2, by means of the Julia–Kocienski type coupling reaction between a C2 symmetrical A ring ketone and a CD ring synthon. The effect of C2 substituents on the stereoselectivity of the coupling reaction was evaluated. The biological activities of the synthesized derivatives were evaluated in an HL-60 cell-based assay. The a-methoxy-substituted C2α-7a was found to show potent cell-differentiating activity, with an ED50 value of 0.38 nM, being 26-fold more potent than 1,25D3.

scholarly journals Synthetic Chiral Derivatives of Xanthones: Biological Activities and Enantioselectivity Studies

Molecules ◽  
2019 ◽  
Vol 24 (4) ◽  
pp. 791 ◽  
Author(s):  
Carla Fernandes ◽  
Maria Carraro ◽  
João Ribeiro ◽  
Joana Araújo ◽  
Maria Tiritan ◽  
...  
Keyword(s):  
Biological Activity ◽  
Biological Activities ◽  
Pharmacological Activities ◽  
Sar Studies ◽  
Naturally Occurring ◽  
Structure Activity ◽  
Wide Range ◽  
Synthetic Methodologies ◽  
Derivatives Of ◽  
Biological And Pharmacological Activities

Many naturally occurring xanthones are chiral and present a wide range of biological and pharmacological activities. Some of them have been exhaustively studied and subsequently, obtained by synthesis. In order to obtain libraries of compounds for structure activity relationship (SAR) studies as well as to improve the biological activity, new bioactive analogues and derivatives inspired in natural prototypes were synthetized. Bioactive natural xanthones compromise a large structural multiplicity of compounds, including a diversity of chiral derivatives. Thus, recently an exponential interest in synthetic chiral derivatives of xanthones (CDXs) has been witnessed. The synthetic methodologies can afford structures that otherwise could not be reached within the natural products for biological activity and SAR studies. Another reason that justifies this trend is that both enantiomers can be obtained by using appropriate synthetic pathways, allowing the possibility to perform enantioselectivity studies. In this work, a literature review of synthetic CDXs is presented. The structures, the approaches used for their synthesis and the biological activities are described, emphasizing the enantioselectivity studies.

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.

Design, synthesis and biological activities of pyrrole-3-carboxamide derivatives as EZH2 (enhancer of zeste homologue 2) inhibitors and anticancer agents

2020 ◽  
Vol 44 (6) ◽  
pp. 2247-2255
Author(s):  
Qifan Zhou ◽  
Lina Jia ◽  
Fangyu Du ◽  
Xiaoyu Dong ◽  
Wanyu Sun ◽  
...  
Keyword(s):  
Biological Activity ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Activity Assay ◽  
Design Synthesis ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Enhancer Of Zeste

A novel series of pyrrole-3-carboxamides targeting EZH2 have been designed and synthesized. The structure–activity relationships were summarized by combining with in vitro biological activity assay and docking results.

Antinociceptive Activity and Preliminary Structure-Activity Relationship of Chalcone-Like Compounds

2008 ◽  
Vol 63 (11-12) ◽  
pp. 830-836 ◽  
Author(s):  
Rogério Corrêa ◽  
Bruna Proiss Fenner ◽  
Fátima de Campos Buzzi ◽  
Valdir Cechinel Filho ◽  
Ricardo José Nunes
Keyword(s):  
Biological Activity ◽  
Biological Activities ◽  
Antinociceptive Effect ◽  
Experimental Models ◽  
Antinociceptive Activity ◽  
Dominant Factor ◽  
Writhing Test ◽  
Aromatic Ketones ◽  
Structure Activity ◽  
Relationship Of

Abstract Chalcones belong to a class of α,β unsaturated aromatic ketones which occur abundantly in nature, especially in plants. They are promising and interesting compounds due to their vast applications in pharmaceuticals, agriculture and industry. Several studies have shown that these compounds exert important biological activities in different experimental models. The present work deals with the antinociceptive activity, evaluated against the writhing test, of three series of chalcone-like compounds obtained by the Claisen-Schmidt condensation, using different aldehydes and substituted acetophenones. The results reveal that the compounds synthesized show a significant antinociceptive effect compared with nonsteroidal drugs such as aspirin, paracetamol and diclofenac. They also show that the electronic demand of the substituents is the dominant factor of the biological activity.

Chemistry and Anticancer Activity of Hybrid Molecules and Derivatives Based on 5-Fluorouracil

2021 ◽  
Vol 28 ◽  
Author(s):  
Wilson Cardona-G ◽  
Angie Herrera-R ◽  
Wilson Castrillón-L ◽  
Howard Ramírez-Malule
Keyword(s):  
Side Effects ◽  
Anticancer Activity ◽  
Antitumor Agents ◽  
Biological Activities ◽  
Hybrid Molecule ◽  
Drug Discovery And Development ◽  
Promising Strategy ◽  
Structure Activity ◽  
Hybrid Molecules ◽  
Sar Analysis

: Cancer still continues as an important cause of death worldwide. Thus, several conventional anticancer treatments are widely used, however, most of them display low selectivity against malignant cells and induce many adverse side effects. Among these, the use of therapies based on 5-Fluorouracil (5-FU) has been one of the most efficient, with a broad-spectrum. Due to these circumstances, various modifications of 5-FU have been developed to improve drug delivery and reduce side effects. Among the optimization strategies, modifications of 5-FU at N1 or N3 position are made, usually including incorporation of pharmacological active compounds with anticancer activity (called hybrid molecule) and functionalization with other groups of compounds (called conjugates). Several studies have been conducted in the search for new alternative therapies against cancer, many of them have evidenced that hybrid compounds exhibit good anticancer activity, which has emerged as a promising strategy in this field of drug discovery and development. Furthermore, the binding of 5-FU to amino acids, peptides, phospholipids, polymers, among others, improves metabolic stability and absorption. This review highlights the potential of hybrids and derivatives based on 5-FU as a scaffold for the development of antitumor agents, besides, it also presents a detailed description of the different strategies employed to design and synthesized these compounds, together with their biological activities and Structure-Activity Relationship (SAR) analysis.

Progress and development of C-3, C-6, and N-9 position substituted carbazole integrated molecular hybrid molecules as potential anticancer agents

2021 ◽  
Vol 21 ◽  
Author(s):  
Pratibha Mehta Luthra ◽  
Nitin Kumar
Keyword(s):  
Biological Activity ◽  
Side Effects ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Structural Motif ◽  
Hybrid Compounds ◽  
Hybrid Molecules ◽  
Anticancer Mechanism ◽  
Pharmacologically Active

Abstract: The carbazole skeleton, a key structural motif occurring naturally or chemically synthesized, have shown various biological activities. Molecular hybridization based on the combination of two or more bioactive pharmacophores has been an important tool to convert the potent structural leads to form new hybrid compounds with improved biological activity. In recent years, modifications/substitutions of the carbazole motif at C3, C6, N9 position have been carried to develop novel carbazole based potential anticancer agents in the cancer therapy. In the last fifteen years, several compounds based on carbazole core integrated to pharmacologically active molecular hybrid having active pharmacophore such as 1,3,4-thiadiazole, thiazole, guanidine, sulfonamides, glyoxamides, imidazole, phenanthrene, rhodamine, chalcones, imidazopyridine, platinum 2H-chromen-2-one, hydrazones, piperazine, Isoxazole-thiadiazole, pyrazole etc. have been synthesized showing anticancer profile at sub-micromolar to nano-molar concentrations. We have thoroughly reviewed the design, progress and development of C-3, C-6, and N-9 position substituted carbazole derivatives integrated with various medicinally active pharmacophore as potential anticancer agents evaluated against various cancer cell lines. Additionally, the anticancer mechanism and in vivo activity of the reported compounds have been discussed. This study will support in designing of a new pharmacophore that can be linked to carbazole motif for development for new, potent and target specific anticancer drugs with improved pharmacokinetics and minimal side effects.

scholarly journals Usnic acid biological activity: history, evaluation and usage

2017 ◽  
Vol 6 (12) ◽  
pp. 2752 ◽  
Author(s):  
Ahlam Abdulaziz Alahmadi
Keyword(s):  
Biological Activity ◽  
Side Effects ◽  
Inflammatory Pain ◽  
Biological Activities ◽  
Usnic Acid ◽  
High Dose ◽  
Fatty Tissue ◽  
Wide Availability ◽  
Species Being ◽  
Lichen Metabolite

Since Usnic acid (UA) was isolated from lichen metabolite in 1844, a lot of studies were conducted on it and now it became commercially available in the market. Its wide availability in different lichen species, being isolated easily, and high purity of the isolated product make it an excellent base for producing new pharmaceuticals. In this review the different usage of UA was summarized. It was utilized as an antioxidant, anti-proliferative, antimicrobial and antiprotozoal, larvicidal and insecticidal, antifungal, antiviral, algicidal, anti-inflammatory, pain-relieving and antipyretic agent. Many adverse effects were associated with using usnic acid, especially at high dose, including; hepatotoxicity, genotoxicity, allergenicity, side effects on the cardiovascular system and adipocytes of fatty tissue. This review aimed to throw the light on the updated biological activities, effectiveness and safety and usage of usnic acid during the last decade.

The History and Development of Quantitative Structure-Activity Relationships (QSARs)

2017 ◽  
Vol 2 (2) ◽  
pp. 36-46 ◽  
Author(s):  
John C. Dearden
Keyword(s):  
Molecular Structure ◽  
Biological Activity ◽  
Molecular Descriptors ◽  
Biological Activities ◽  
Molecular Size ◽  
Liquid Viscosity ◽  
Quantitative Structure ◽  
Structure Activity ◽  
The Subject ◽  
Quantitative Structure Activity Relationships

Following the publication of the history and development of QSAR, it became apparent that a number of matters had not been covered. This addendum is an attempt to rectify that. A very early approach (ca. 60 B.C.) by Lucretius shows that he understood how molecular size and complexity affect liquid viscosity. Comments by Kant (1724-1804) emphasized the necessity of mathematics in science. A claim that the work of von Bibra and Harless in 1847 pre-dated that of Overton and H.H. Meyer is shown not to be correct. K.H. Meyer and Gottlieb-Billroth published in 1920 what is probably the first QSAR equation. Brown, who with his co-author Fraser is credited with the first definitive recognition in 1868-9 that biological activity is a function of molecular structure, is often cited as Crum Brown; in fact, Crum was his second given name. The QSAR work of the Soviet chemist N.V. Lazarev in the 1940s was far ahead of his time, showing numerous correlations of biological activities and physicochemical properties with molecular descriptors. The subject of inverse QSAR is discussed.

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