Current Issue : October - December Volume : 2017 Issue Number : 4 Articles : 5 Articles
Parasitic diseases are a public health problem affecting millions of people worldwide. One\nof the scaffolds used in several drugs for the treatment of parasitic diseases is the benzimidazole\nmoiety, a heterocyclic aromatic compound. This compound is a crucial pharmacophore group\nand is considered a privileged structure in medicinal chemistry. In this study, the benzimidazole\ncore served as a model for the synthesis of a series of 2-(2-amino-5(6)-nitro-1H-benzimidazol-1\n-yl)-N-arylacetamides 1ââ?¬â??8 as benznidazole analogues. The in silico pharmacological results calculated\nwith PASS platform exhibited chemical structures highly similar to known antiprotozoal drugs.\nCompounds 1ââ?¬â??8 when evaluated in silico for acute toxicity by oral dosing, were less toxic than\nbenznidazole. The synthesis of compounds 1ââ?¬â??8 were carried out through reaction of 5(6)-nitro-\n1H-benzimidazol-2-amine (12) with 2-chlroactemides 10aââ?¬â??h, in the presence of K2CO3 and acetonitrile\nas solvent, showing an inseparable mixture of two regioisomers with the -NO2 group in position 5\nor 6 with chemical yields of 60 to 94%. The prediction of the NMR spectra of molecule 1 coincided\nwith the experimental chemical displacements of the regioisomers. Comparisons between the NMR\nprediction and the experimental data revealed that the regioisomer endo-1,6-NO2 predominated in\nthe reaction. The in vitro antiparasitic activity of these compounds on intestinal unicellular parasites\n(Giardia intestinalis and Entamoeba histolytica) and a urogenital tract parasite (Trichomonas vaginalis)\nwere tested. Compound 7 showed an IC50 of 3.95 Ã?¼Mand was 7 time more active against G. intestinalis\nthan benznidazole. Compounds 7 and 8 showed 4 times more activity against T. vaginalis compared\nwith benznidazole....
1,4-Pentadien-3-one derivatives derived from curcumin possess excellent inhibitory activity\nagainst plant viruses. On the basis of this finding, a series of novel 1,4-pentadien-3-one derivatives\ncontaining a 1,3,4-thiadiazole moiety were designed and synthesized, and their structures confirmed\nby IR, 1H-NMR, and 13C-NMR spectroscopy and elemental analysis. The antiviral activities of\nthe title compounds were evaluated against tobacco mosaic virus (TMV) and cucumber mosaic\nvirus (CMV) in vivo. The assay results showed that most of compounds had remarkable antiviral\nactivities against TMV and CMV, among which compounds 4b, 4h, 4i, 4k, 4o, and 4q exhibited good\ncurative, protection, and inactivation activity against TMV. Compounds 4h, 4i, 4k, 4l, 4o, and 4q\nexhibited excellent protection activity against TMV, with EC50 values of 105.01, 254.77, 135.38, 297.40,\n248.18, and 129.87 �¼g/mL, respectively, which were superior to that of ribavirin (457.25 �¼g/mL).\nIn addition, preliminary SARs indicated that small electron-withdrawing groups on the aromatic\nring were favorable for anti-TMV activity. This finding suggests that 1,4-pentadien-3-one derivatives\ncontaining a 1,3,4-thiadiazole moiety may be considered as potential lead structures for discovering\nnew antiviral agents....
Protein disulfide isomerase (PDI) is a member of the thioredoxin superfamily of redox enzymes. PDI is a multifunctional protein\nthat catalyzes disulfide bond formation, cleavage, and rearrangement in unfolded or misfolded proteins and functions as a\nchaperone in the endoplasmic reticulum. Besides acting as a protein folding catalyst, several evidences have suggested that PDI can\nbind small molecules containing, for example, a phenolic structure, which includes the estrogenic one. Increasing studies indicate\nthat PDI is involved in both physiology and pathophysiology of cells and tissues and is involved in the survival and proliferation of\ndifferent cancers. Propionic acid carbamoyl methyl amides (PACMAs) showed anticancer activity in human ovarian cancer, both\nin vitro and in vivo, by inhibiting PDI.The inhibition of PDIââ?¬â?¢s activity may have a therapeutic role, in various diseases, including\ncancer. In the present study, we designed and synthesized a diversified small library of compounds with the aim of identifying a new\nclass of PDI inhibitors. Most of synthesized compounds showed a good inhibitory potency against PDI and particularly 4-methyl\nsubstituted 2,6-di-tert-butylphenol derivatives (8ââ?¬â??10) presented an antiproliferative activity in a wide panel of human cancer cell\nlines, including ovarian ones....
Esters based on mono- and bicyclic terpenoids with glycine have been synthesized via\nSteglich esterification and characterized by 1H-NMR, IR, and mass spectral studies. Their analgesic\nand anti-inflammatory activities were investigated after transdermal delivery on models of formalin,\ncapsaicin, and AITC-induced pain, respectively. Glycine esters of menthol and borneol exhibited\nhigher antinociceptive action, whereas eugenol derivative significantly suppressed the development\nof the inflammatory process. The mechanism of competitive binding between terpenoid esters\nand TRPA1/TRPV1 agonists was proposed explaining significant analgesic effect of synthesized\nderivatives. For an explanation of high anti-inflammatory activity, competitive inhibition between\nterpenoid esters and AITC for binding sites of the TRPA1 ion channel has been suggested....
Background: Replacement of chloride ions in cyanuric chloride give several variants of 1,3,5-triazine derivatives\nwhich were investigated as biologically active small molecules. These compounds exhibit antimalarial, antimicrobial,\nanti-cancer and anti-viral activities, among other beneficial properties. On the other hand, treatment of bacterial\ninfections remains a challenging therapeutic problem because of the emerging infectious diseases and the increasing\nnumber of multidrug-resistant microbial pathogens. As multidrug-resistant bacterial strains proliferate, the necessity\nfor effective therapy has stimulated research into the design and synthesis of novel antimicrobial molecules.\nResults: 1,3,5-Triazine 4-aminobenzoic acid derivatives were prepared by conventional method or by using microwave\nirradiation. Using microwave irradiation gave the desired products in less time, good yield and higher purity.\nEsterification of the 4-aminobenzoic acid moiety afforded methyl ester analogues. The s-triazine derivatives and their\nmethyl ester analogues were fully characterized by FT-IR, NMR (1H-NMR and 13C-NMR), mass spectra and elemental\nanalysis. All the synthesized compounds were evaluated for their antimicrobial activity. Some tested compounds\nshowed promising activity against Staphylococcus aureus and Escherichia coli.\nConclusions: Three series of mono-, di- and trisubstituted s-triazine derivatives and their methyl ester analogues\nwere synthesized and fully characterized. All the synthesized compounds were evaluated for their antimicrobial activity.\nCompounds (10), (16), (25) and (30) have antimicrobial activity against S. aureus comparable to that of ampicillin,\nwhile the activity of compound (13) is about 50% of that of ampicillin. Compounds (13) and (14) have antimicrobial\nactivity against E. coli comparable to that of ampicillin, while the activity of compounds (9ââ?¬â??12) and (15) is about 50%\nof that of ampicillin. Furthermore, minimum inhibitory concentrations values for clinical isolates of compounds (10),\n(13), (14), (16), (25) and (30) were measured. Compounds (10) and (13) were more active against MRSA and E. coli\nthan ampicillin. Invitro cytotoxicity results revealed that compounds (10) and (13) were nontoxic up to 250 Ã?¼g/mL\n(with SI = 10) and 125 Ã?¼g/mL (with SI = 5), respectively....
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