Structure-function relationship of substituted bromomethylcoumarins in nucleoside specificity of RNA alkylation

Selective alkylation of RNA nucleotides is an important field of RNA biochemistry, e.g. in applications of fluorescent labeling or in structural probing experiments, yet detailed structure-function studies of labeling agents are rare. Here, bromomethylcoumarins as reactive compounds for fluorescent labeling of RNA are developed as an attractive scaffold on which electronic properties can be modulated by varying the substituents. Six different 4-bromomethyl-coumarins of various substitution patterns were tested for nucleotide specificity of RNA alkylation using tRNA from Escherichia coli as substrate. Using semi-quantitative LC-MS/MS analysis, reactions at mildly acidic and slightly alkaline pH were compared. For all tested compounds, coumarin conjugates with 4-thiouridine, pseudouridine, guanosine, and uridine were identified, with the latter largely dominating. This data set shows that selectivity of ribonucleotide alkylation depends on the substitution pattern of the reactive dye, and even more strongly on the modulation of the reaction conditions. The latter should be therefore carefully optimized when striving to achieve selectivity. Interestingly, the highest selectivity for labeling of a modified nucleoside, namely of 4-thiouridine, was achieved with a compound whose selectivity was somewhat less dependent on reaction conditions than the other compounds. In summary, bromomethylcoumarin derivatives are a highly interesting class of compounds, since their selectivity for 4-thiouridine can be efficiently tuned by variation of substitution pattern and reaction conditions

Synthesis and Oral Hypoglycemic Activity of 3-[5'-Methyl-2'-aryl-3'-(thiazol-2ʺ-yl amino) thiazolidin-4'-one]coumarin Derivatives

Number of heterocyclic compounds has been exploited to develop pharmaceutically important molecules, out of which biheterocyclic coumarins are clinically used potential drug candidates showing oral hypoglycemic and antidiabetic activities. A new series of 3-[5'-methyl-2'-aryl-3'-(thiazol-2ʺ-yl amino)thiazolidin-4'-one]coumarin derivatives were designed and synthesized. The title compounds were synthesized from starting material 3- acetyl coumarin. All the synthesized compounds were characterized and screened for hypoglycemic activity. Some of the compounds exhibited promising activity

Benzimidazole-Urea derivatives as anti-cancer agents: In-silico study, synthesis and in-vitro evaluation

A new series of urea derivatives containing benzimidazole group as potential anticancer agents have been designed and synthesized. The structures of the synthesized compounds were characterized and confirmed by spectroscopic techniques such as 1H NMR, and Mass spectrometry. A new series of urea derivatives containing benzimidazole group were design with an intention to search new antiproliferative lead compound. Drug like properties and bioactivity score for drug targets of designed compounds were calculated by molinspiration tool and obtained result found to obey Lipinski’s rule that indicates the compound are orally active molecules. Osiris property explorer was used for the prediction of drug relevant properties and toxicity of synthetic compounds. Pre ADMET server was also used to estimate ADME properties of synthetic compounds, results showed good to notable anticancer activity. So that, these new benzimidazole-urea compounds could serve as potential template to become leads in near future for the discovery and development of new effect orally drugs molecules

Synthesis and Oral Hypoglycemic Activity of 3-[5'-Methyl-2'-aryl-3'- (thiazol-2''-yl amino)thiazolidin-4'-one]coumarin Derivatives. E-Journal of Chemistry

Abstract: Number of heterocyclic compounds has been exploited to develop pharmaceutically important molecules, out of which biheterocyclic coumarins are clinically used potential drug candidates showing oral hypoglycemic and antidiabetic activities. A new series of 3-[5'-methyl-2'-aryl-3'-(thiazol-2''-yl amino)thiazolidin-4'-one]coumarin derivatives were designed and synthesized. The title compounds were synthesized from starting material 3-acetyl coumarin. All the synthesized compounds were characterized and screened for hypoglycemic activity. Some of the compounds exhibited promising activity

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1749-1760Structural and physicochemical requirements of aryl carboxylic acid amide derivatives for the inhibition of human dihydroorotate dehydrogenase (hDHODH) are explored in this QSAR study. The calculated molecular descriptors (electronic and thermodynamic) have been used to derive QSAR models between hDHODH inhibitory activity and structural properties. The best model for prediction of hDHODH inhibitory activity is obtained by applying sequential multiple linear regression (SMLR) analysis.  Regression coefficient of all the descriptors is significant at more than 99% and statistically significant model with r2 > 0.87 is obtained. Selected QSAR model emphasized the importance of logP, torsion energy (Et), 1,4-dihedral van der Waals interaction (1,4-VDWE) and <span style="mso-bidi-font-weight: bold">electronic descriptor like lowest unoccupied molecular orbital (LUMO) on hDHODH inhibitory activity. Results of QSAR analysis show that logP and LUMO are the principle descriptors for inhibition of hDHODH. QSAR model has also been tested successfully for internal (q2 > 0.753) and external (r2 pred > 0.621) validation criteria. It is believed that the results of this study will be helpful in the design of more potent and selective <i style="mso-bidi-font-style: normal">hDHODH inhibitors. </span

Synthesis and anti-inflammatory activity of 4-(5'-acetyl-6'-hydroxy -3'-methyl-benzofuran-2'-yl) coumarin and 6-acetyl-3, 7-dimethyl-2-(coumarin-4'-yl) furo [3,2-<i style="">g</i>] chromen-5-one

1674-1678Various 4-bromomethylcoumarins 1 have been reacted with diacetyl resorcinol 2 to afford corresponding ethers 3, which undergo intermolecular aldol condensation followed by dehydration to form 4-(5'-acetyl-6'-hydroxy-3'-methylbenzofuran-2'-yl) coumarin 4. Further compound 4 on reaction with sodium acetate and acetic anhydride afford 6-acetyl-3, 7-dimethyl-2-(coumarin 4'-yl) furo [3,2-g] chromen-5-one 5. Their structures have been confirmed by IR, NMR and mass spectral data. Of these compounds, 4e, 4f and 5e show good anti-inflammatory and analgesic activity

Microwave Assisted Liquid Phase Synthesis of Benzimidazolo Benzothiophenes for Antimicrobial Activity

Benzimidazolo benzothiophene derivatives were prepared by liquid phase combinatorial synthesis using soluble polymer support PEG 5000 and 4-fluoro-3-nitrobenzoic acid as starting materials with substituted primary amines. All these synthesized compounds were established by the spectral data and tested for antimicrobial activity against gram positive bacteria, i.e. S. aureus, B. subtilis and gram negative bacteria, E.coli and P.aeruginosa and anti fungal activity against C. albicans. Ampicillin and ciprofloxacin were used as standard for antibacterial activity and cotrimoxazole for anti fungal activity. Compared with standards compounds (1a-h) showed significant activity against bacterial species and 1g showed significant activity against fungal species

Dual fluorescence and biological evaluation of paracetamol ethers from 4-bromomethylcoumarins

2416-2422Paracetamol 1 has been reacted with 4-bromomethylcoumarins 2 to obtain the corresponding ethers 3 which have been hydrolyzed to the amino ethers 4. Structure of 4 has been confirmed by the chemoselective reaction of 2 with p-aminophenol, which has also been found to yield the thermodynamically controlled products 5 at elevated temperatures. Compounds 3 have been found to exhibit dual fluorescence. IR,1H NMR and mass spectral data have confirmed structures of all the compounds. Biological evaluation has shown that compounds 3e and 3g show good anti-inflammatory and analgesic properties

Design, synthesis and antimicrobial activities of some novel 1,3,4-thiadiazole, 1,2,4-triazole-5-thione and 1,3-thiazolan-4-one derivatives of benzimidazole

A series of novel 1,3,4-thiadiazole; 1,2,4-triazole-5-thione and 1,3-thiazolan-4-one derivatives of benzimidazole were synthesized by nucleophilic substitution reaction of 2-substituted-1[H] benzimidazole. Compounds (1H-benzo[d]imidazol-2-yl)methanamine 3, 2-(isothiocyanatomethyl)-1H-benzo[d]imidazole 4, 4-(1H-benzo[d]imidazol-2-yl)benzenamine 6 and 4-(1H-benzo[d]imidazol-2-yl)benzenamine 7 are synthesized for the synthesis of targeted compounds. Structures of all the targeted synthesized compounds were evaluated by spectral and elemental methods of analysis. All the synthesized compounds were evaluated for antibacterial and antifungal activities. Some of the synthesized compounds showed good antibacterial and antifungal activities with 2.0 and 2.5 μg/mL MIC (minimum inhibitory concentration), respectively