Andits Derivatives Research Articles

Molecular Dynamic Simulation and 3d-pharmacophore Modeling of Alpha Mangostin and Its Derivatives against Estrogen Alpha Receptor

Background: Human estrogen receptor alpha (ERα), which is known to play a role in mediating cell proliferation, metastasis, and resistance to apoptosis, is one of the targets of breast cancer therapies. Alpha mangostin (AM) is an active xanthone compound from Garcinia mangostana L. which has activity as an ERα inhibitor. Objectives: This research aims to predict the pharmacokinetic and toxicity, and to study the molecular interactions of AM derivatives with the ERα using computer-aided simulation approaches through molecular docking, molecular dynamic, and pharmacophore screening to develop novel anti-breast cancer agents. Methods: Marvinsketch and Chimera programs were used to design and optimize the structure of AM and its derivatives. For screening the pharmacokinetic and toxicity profiles, the PreADMET web was used. The AutoDockTools 1.5.6 and LigandScout 4.4.3 Advanced software were used to conduct the molecular docking simulation and pharmacophore screening, respectively, while the molecular dynamic simulation was performed using AMBER 16. The results were visualized by Biovia Discovery Studio. Results: Molecular docking using Autodock showed that FAT10 derivate has lower binding free energy (ΔG) (-12.04 kcal/mol) than AM (-8.45 kcal/mol) when docking to ERα and both performed the same hydrogen bond with Thr347. These support the results of the MMPBSA calculation on dynamic simulation which shows FAT10 (-58.4767 kcal/mol) has lower ΔG than AM (-42.7041 kcal/mol) and 4-OHT (- 49.0821 kcal/mol). The pharmacophore screening results also showed that FAT10 fitted the pharmacophore with a fit score of 47.08. Conclusion: From the results, it can be suggested that FAT10 has promising activity as ERα antagonist. Further in vitro and in vivo experiments should be carried out to support these in silico studies.

Osthole: A Medicinally Privileged Natural Compound with its Therapeutic Potential

Abstract:: Osthole is a coumarin derived natural compound which is an essential ingredient of Traditional Chinese Medicine (TMC) and is widely distributed in nature in plants like Cnidium monnieri (L) Cusson and Angelica pubescens. Current study presents a critical review on description of pharmacological importance of osthole, which is reported to exhibit anticancer, antioxidant, osteogenic, hepatoprotective, neuroprotective, cardiovascular protective, antimicrobial, immuno-modulatory and anti-inflammatory activities. Till date, the reports include pharmacological properties, brief chemistry of advanced methods to explore osthole content in variety of plants. Present review seeks to highlight the sources, biosynthesis, extraction methods, pharmacological properties of the molecule and its derivatives. A brief discussion on patents recently published and granted on the molecule has also been highlighted. Thus the overview of the literature presents the analysis about future possible modalities of the research on this molecule.

The Effects of Curcuma longa and its Derivative Curcumin on Aspergillus Infections: A Systematic Review

Background and Purpose: Curcuma longa L. is one of the most important medicinal plants used in traditional medicine. Its main compound, curcumin, has been widely reported for its biological properties. Here, we performed a systematic review of the effects of C. longa L. and its derivative curcumin on Aspergillus infections. Although some limitations in this systematic review study have been identified such as (i) the number of studies evaluating the efficacy of turmeric and its derivatives, such as curcumin, in fungal diseases such as Aspergillus is very small, and further in vitro and in vivo studies should be performed to better evaluate the efficacy of the plant; (ii) studies of the effects of turmeric and curcumin in different countries; (iii) the duration of treatment for in vivo studies was 2 to 12 weeks, so longer treatment intervals and longer duration are needed to better evaluate the treatment. Materials and Methods: In this review article, antifungal effects of C. longa and its derivative curcumin on the different strains of Aspergillus are discussed. The study data were obtained from various databases, including Scopus, PubMed, Web of Science, Embase and Google Scholar, which were published by December 2019. The main criterion for entering data into the survey data was access to the English abstract at the search stage. The keywords used in the search included C. longa, curcumin, antifungal effect and Aspergillus. Of the 2,500 studies in the initial search, only 15 qualified for study inclusion, among which 9 (60%) were performed on the effect of curcumin against Aspergillus spp. The other 6 studies (40%) had focused on the antifungal effect of C. longa. Moreover, 9 studies (60%) were performed in vitro, 4 studies (27%) were performed in vivo and 2 studies (13%) were performed both in vivo and in vitro. Results: Studies have shown that C. longa has a significant effect on the development of the majority of microorganisms. Its predominant metabolite, curcumin, plays a major role in the biological activities of C. longa. Conclusion: Due to increased drug resistance, particularly antifungal, curcumin and its derivatives may be an appropriate option for the treatment of aspergillosis infections.

Design, Synthesis and In Vitro Biological Evaluation Of N-(2-Aminophenyl)-3-Quinolin-4-yl -Prop-2-enamide Derivatives As Novel Colon Anticancer Agents

Acetylation and deacetylation of histone proteins is regulated through two enzymes; acetylation is mediated through histone acetyl transferase (HAT) whereas deacetylation is mediated through histone deacetylase (HDAC). Histone deacetylase removes acetyl group of lysine residue on histone proteinthis makes negatively charged histone able to bind with DNA containing positive centers. In this way DNA remain in compact form with histone proteins. Therefore the transcription or replication enzymes and cofactors not able to bind such compact DNA structure. Histone deacetylase inhibition results into inhibition of various transcription activities which may get accelerated during cancer development. The aim of proposed study is to develop effective isoform selective Histone deacetylase inhibitor. Synthesis of N-(2-Aminophenyl)-3-Quinolin-4-yl-Prop-2-Enamide derivatives from isatin and its derivatives was achieved. Synthesis was carried out in two steps with good yield. 21 Compounds were synthesized and found to be effective with IC50s in between 3.694 - 38.4µmol in human HCT-116, COLO 205 and COLO 320 DM colon cancer cells in vitro. For the cytotoxicity activity study MTT assay method was adopted. Docking studies were performed initially with HDAC8 enzyme using V-life MDS software for synthesized compounds and had selected best fit molecules for synthesis. The synthesized molecules are effective as colon anticancer agents.

SEPARATION PROCESS OF ROSMARINIC ACID AND THEIR DERIVATIVES FROM CELASTRUS HINDSII BENTH LEAVES

Rosmarinic acid is a naturally antioxidant, which is biosynthesized from the amino acids Lphenylalanineand L-tyrosine by eight enzymes that include phenylalanine ammonia lyase andcinnamic acid 4-hydroxylase. Rosmarinic acid can also be chemically produced by theesterification of caffeic acid and 3,4-dihydroxyphenyllactic acid. Recently, rosmarinic acid andits derivatives (RA) have attracted interests for their biological activities, which include antiinflammatory,anti-oxidant, anti-angiogenic, anti-tumor, and anti-microbial functions. RAextraction procedure from Xaden leaves Celastrus hindsii was investigated. RA extracts wereobtained from 50 % ethanol extract. The optimal conditions for extraction were as followings:solvent/material ratio 12/1 (v/m), two time extractions, and total extraction time of 3 hours. RAextracts were refined by Diaion HP-20column to have RA with 83.30 % purity and yield 2.86 %(by dry weight material).

Dihydroartemisinin-induced inhibition of proliferation in BEL-7402 cells: An analysis of the mitochondrial proteome

Artemisinin, the active ingredient of the Chinese medicinal herb Artemisia annua L., and its derivatives (ARTs) are currently widely used as anti-malarial drugs around the world. In this study, we found that dihydroartemisinin (DHA), one of the main active metabolites of ARTs, inhibited the proliferation of human hepatocarcinoma BEL-7402 cells in a concentration-dependent manner. To interpret the mechanisms involved, an analysis of the mitochondrial proteome was performed employing two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Seven mitochondrial proteins including fumarate hydratase, 60 kDa heat shock protein, enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, two subunits of ATP synthase and NADPH:adrenodoxin oxidoreductase were identified to be differentially expressed between the control and DHA-treated groups. Our results indicate that the imbalance of energy metabolism induced by DHA may contribute, at least in part, to its anti-cancer potential in BEL-7402 cells.

Controlled assembly of large π-conjugated n-type molecules on Au(111)

Controlled assemblies of the n-type 5,6,11,12,17,18-hexaazatrinaphthylene (HATNA) molecule andits derivatives, 5,6,11,12,17,18-hexaazatrinaphthylene-2,8,14-tricarboxylic acid (HATNA–COOH)and 2,8,14-tri(3,4,5-tridodecyloxyphenylaminocarbonyl)-5,6,11,12,17,18-hexaazatrinaphthylene(HATNA-den), on Au(111) electrodes have been investigated using electrochemical scanningtunneling microscopy (ECSTM). Orientations of HATNA and HATNA–COOH moleculeson Au(111) electrodes can be manipulated with potential modulation and imaged in situ byECSTM. By increasing the applied electrode potentials, the HATNA and HATNA–COOHmolecules were tuned at the solid/liquid interface to orient from parallel to perpendicularto the electrode surface because of dominating adsorbate–adsorbate interactions such asπ–π stacking, hydrogen bonding, and weak dipole–dipole interactions and deprotonationof –COOH groups of the HATNA–COOH molecule at higher positive potentials.However, a stable adsorption orientation independent of applied electrode potentialswas observed for the tridendron-containing molecule HATNA-den due to stronginteractions between the alkyl chains and the Au(111) substrate, and betweenπ-electrons of the aromatic rings and the Au(111) substrate. The ability to orient adsorbatesand to change surface structures by controlling the substrate potential is a great boon tothose attempting to create designer two-dimensional structures.

Formation of racemic compound crystals by mixing of two enantiomeric crystals in the solid state. Liquid transport of molecules from crystal to crystal

Mixing of powdered (-)- and (+)-enantiomer crystals in the solid state gives crystals of the racemic compound. This racemic crystal formation was followed by IR spectral measurement of a 1∶1 mixture of (-)- and (+)-enantiomer crystals as a Nujol mull. As the formation of racemic crystals proceeds, the OH absorptions of the enantiomer disappear gradually and new OH absorptions due to the racemic compound appear. The formation of racemic crystals from enantiomer crystals has been studied for various kinds of chiral compounds: 2,2′-dihydroxy-1,1′-binaphthyl (1) and its derivatives, 10,10′-dihydroxy-9,9′-biphenanthryl (4), 2,2′-dihydroxy-4,4′,6,6′-tetramethylbiphenyl (5) and its derivatives, 4,4′-dihydroxy-2,2′,3,3′,6,6′-hexamethylbiphenyl (8), 1,6-di(o-chlorophenyl)-1,6-diphenylhexa-2,4-diyne-1,6-diol (11) and its derivatives, trans-4,5-bis[hydroxy(diphenyl)methyl]-2,2-dimethyl-1,3- dioxacyclopentane (17) and its derivatives, tartaric acid (20) dimethyl tartrate (21), malic acid (22), mandelic acid (23), and norephedrine (24). These molecular movements and blending occur rapidly in the presence of liquids such as liquid paraffin (Nujol), seed oils such as olive, coconut, rapeseed and soybean oil, artificial oil such as silicone oil and water, although the same movement also occurs in the absence of the liquid. For example, keeping a mixture of powdered (-)-1 (1a) and (+)-1 (1b) at room temperature for 48 h gives racemic crystals (1c). However, molecular aggregation sometimes occurs in solution but not in the solid state. For example, recrystallization of (-)-16 (16a) and (+)-16 (16b) from solvent gives racemic crystals of 16c, although mixing of these two components as powders in the presence of liquid does not give 16c. In order to determine the mechanism of the molecular movement in the solid state, X-ray crystal structures of optically active and racemic compounds and also the molecular movements from optically active crystal to racemic crystal have been studied.

Use of lithium (α-methylbenzyl)allylamide for a formal asymmetric synthesis of thienamycin

The highly stereoselective conjugate addition of lithium (αR)-(α-methylbenzyl)allylamide 3 to (E)-tert-butyl penta-2,4-dienoate 4, followed by a stereoselective aldol reaction with acetaldehyde, are the key steps in the synthesis of the known β-lactam intermediate, (3S,4R)-3-[(R)-1-(tert-butyldimethyls ilyloxy)ethyl]-4-vinylazetidin-2-one 2, for elaboration to thienamycin and its derivatives.