Showing papers in "Medicinal Chemistry Research in 2011"

Biological importance of imidazole nucleus in the new millennium

Abstract: Imidazole nucleus is a constituent of many bioactive heterocyclic compounds that are of wide interest because of their diverse biological and clinical applications. This created interest in researchers to synthesize variety of imidazole derivatives and to screen them for their various biological activities viz. anti-cancer, anti-viral, antiHIV, anti-protozoal, anti-mycobacterial, anti-inflammatory, analgesic, anxiolytic, as well anti-diabetic activities.

PASS-assisted exploration of new therapeutic potential of natural products

Abstract: The use of drug substances derived from plants, fungi, bacteria, and marine organisms are “Mother Nature Gift” for diseases of mankind. Many of these are discovered serendipitously and have a long tradition in medicine. Till date, the use of natural products, their semisynthetic and synthetic derivatives have been mostly confined to their ethnic use. But it has been well known that each substance has a wide spectrum of biological activities as evident from some new uses of many old drugs. PASS (Prediction of Activity Spectra for Substances) has been employed as a strong potential tool to predict the biological activity spectrum of synthetic substances for the discovery of new drugs. But the potential of PASS to predict the biological activity spectra of natural products is still underestimated. The present study was therefore undertaken to investigate and correlate the biological activity spectrum of the main phytoconstituent of some selected Indian medicinal plants with their reported biological activities in order to evaluate the applicability of PASS. Further, the unexplored but PASS-predicted activities having good activity score (Pa > 0.7) for particular structure were listed as hidden potential of the plant.

Synthesis, antioxidant evaluation, and quantitative structure–activity relationship studies of chalcones

Abstract: Synthesis, antioxidant activity, and quantitative structure–activity relationship (QSAR) of 25 of chalcone derivatives is reported here. They were synthesized by Claisen–Schmidt reaction and were characterized by FTIR, NMR, and mass spectroscopy. Antioxidant activity is evaluated through four different methods namely, superoxide radical-scavenging, hydrogen peroxide scavenging, reducing power, and DPPH radical-scavenging assays. Generally, compounds with –SCH3 and –OCH3 in the para position of the A-ring and –OH in the B-ring were more active than others. In few cases some of the compounds were more active than ascorbic acid or butylated hydroxytoluene. QSAR was developed correlating the antioxidant activity with the structural features of the compounds and the predictive capability of the models was estimated using internal and external validation methods. All the predictions were within the 99% confidence level. Spatial, structural, and lipophilic properties of the compounds determine their antioxidant properties.

Synthesis and evaluation of in vitro antitubercular activity and antimicrobial activity of some novel 4H-chromeno[2,3-d]pyrimidine via 2-amino-4-phenyl-4H-chromene-3-carbonitriles

Abstract: Novel 5-phenyl-1,5-dihydro-2H-chromeno[2,3-d]pyrimidine-2,4(3H)-dithiones, 5-phenyl-3,5-dihydro-4H-chromeno[2,3-d]pyrimidin-4-ones, 7-phenyl-7,9-dihydro-8H pyrimido[5′,4′:5,6]pyrano[3,2-h]quinolin-8-ones, and 4-amino-5-phenyl-1,5-dihydro-2H-chromeno[2,3-d]pyrimidine-2-thiones were synthesized form 2-amino-4-phenyl-4H-chromene-3-carbonitrile The newly synthesized compounds were characterized by IR, 1H-NMR, 13C-NMR, Mass spectra, and Elemental analysis The compounds were evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv and antibacterial activity against Staphylococcus Aureus [ATCC-25923] and Streptococcus pyogenes [MTCC-443] as Gram-positive, Escherichia coli [ATCC-25922], and Pseudomonas aeruginosa [MTCC-441] as Gram-negative bacterial strains and antifungal activity against Aspergillusniger [MTCC-282] Some of these derivatives exhibited pronounced antitubercular and antimicrobial activities

A rapid access to new coumarinyl chalcone and substituted chromeno[4,3-c]pyrazol-4(1H)-ones and their antibacterial and DPPH radical scavenging activities

Abstract: A series of new coumarin derivatives 4 containing a chalcone moiety were synthesized by condensation of 3-acetyl-4-hydroxycoumarin 1 with aryl or heteroaryl aldehydes 2 in the presence of piperidine in chloroform. The interaction of 3-formyl-4-chloro-coumarin 3 with nitrogen compound nucleophiles are described and lead to the corresponding substituted chromen[4,3-c] pyrazol-4-ones 5. The structures of the obtained compounds were established on the basis of IR|1D|2D NMR, while crystal structure of 3-acetyl-4-hydroxy coumarin 1 was determined using X-ray diffraction and further were evaluated for possible antibacterial and antioxidant activities. The coumarinic chalcone 4d has been found to be the most active (IC50 = 2.07 μM) in this study.

Synthesis and antimicrobial activity of new pyridine derivatives-I

Abstract: 2-Amino substituted benzothiazoles 2a–l and 2-chloropyridine-3-carboxylic acid 3 were used to prepare 2-[N-(substitutedbenzothiazolyl)amino]pyridine-3-carboxylic acids (4a–l) in 2-ethoxy ethanol. Acid chlorides (5a–l) were condensed with 2-hydroxyethyl piperazine (6) and 2,3-dichloropiperazine (7) to prepare amide derivatives 2-[N-(substituted benzothiazolyl)amino]pyridin-3-yl(4-(2-hydroxyethyl)piperazin-1-yl)methanones (8a–l) and 2-[N-(substituted benzothiazolyl) amino]pyridin-3-yl(2,3-dichloropiperazine-1-yl)methanones (9a–l), respectively. The structures of new compounds have been established on the basis of elemental analysis and spectral (IR, 1H NMR, and Mass spectra) studies. The in vitro antimicrobial activity was screened for all the synthesized compounds. Variable and modest activity were observed against the investigated strains of bacteria and fungi.

α-Glucosidase inhibitory and antioxidant properties and antidiabetic activity of Hypericum ascyron L.

Abstract: Different solvent extracts of Hypericum ascyron L. were evaluated by α-glucosidase inhibitory activity and DPPH, ABTS and FRAP assays, respectively, for antioxidant properties in vitro. EtOAC and MeOH extracts showed stronger inhibiting activity against α-glucosidase and rat intestinal α-glucosidase compared with acarbose as positive control. Eight known compounds were isolated from EtOAC and MeOH extracts and screened for α-glucosidase inhibitory and antioxidant activities. Kaempferol and ursolic acid were active compounds of α-glucosidase inhibitory effect in EtOAC extract. Quercetin-3-O-β-d-galactoside, quercetin-3-O-β-d-glucoside and kaempferol from EtOAC and MeOH extracts showed moderate or lightly low antioxidant activity with BHT as positive control. The antidiabetic activity of EtOAC and MeOH extracts was determined in vivo. After intragastric administration of EtOAC extract (500 mg/kg body weight per day) and MeOH extract (500 mg/kg) to groups of on alloxan-induced diabetic mice for 8 days, the level of blood glucose in serum significantly decreased (P < 0.01 and P < 0.05, respectively), the blood lipid level of TC and TG lowered, and the oxidant stress and oxidative damage to tissues were inhibited by decreasing the level of MDA (P < 0.01 and P < 0.01, respectively) and lightly increasing the level of SOD. The result showed that H. ascyron may be a good sources of natural antioxidants and α-glucosidase inhibitor using for the therapy of hyperglycemic and its complication.

Mosquito larvicidal studies of some chalcone analogues and their derived products: structure–activity relationship analysis

Abstract: A series of chalcone analogues and some of their derivatives were synthesized and subjected to the mosquito larvicidal study. Chalcones having electron releasing group(s) on either ring A or ring B showed high toxicity. Electron withdrawing group(s), especially at ring B, reduced the activity of chalcones. The activity was abruptly decreased due to replacement of ring A by CH3, extension of conjugation or blocking of α,β-unsaturated ketone part of chalcones by derivatization. Quantitative structure–activity relationship (QSAR) studies of these compounds were performed using various spatial, electronic and physicochemical parameters. Genetic Function approximation with linear and spline options was used as the chemometric tool for developing the QSAR models.

SnO2 nanoparticles mediated nontraditional synthesis of biologically active 9-chloro-6,13-dihydro-7-phenyl-5H-indolo [3,2-c]-acridine derivatives

Abstract: An efficient, practical, and eco-friendly method of preparation of 9-chloro-6,13-dihydro-7-phenyl-5H-indolo[3,2-c]-acridines (3a–c) is reported by Friedlander condensation of 2-amino-5-chlorobenzophenone 1 and active methylene compound 3,4-dihydro-2H-carbazol-1(9H)-ones (2a–c) in the presence of SnO2 nanoparticles under microwave irradiation Indoloacridines, 3a–c, were screened for their in vitro hemolytic activity, on human erythrocytes and cytotoxicity, on HeLa and Vero cells

Antioxidant activities and UV-protective properties of melanin from the berry of Cinnamomum burmannii and Osmanthus fragrans

Abstract: Cinnamomum burmannii and Osmanthus fragrans are traditional and famous ornamental plants. Melanin-like pigment derived from the berry of C. burmannii (CBM) and O. fragrans (OFM) was isolated with total yield of 0.34 g/100 g and 0.12 g/100 g (wet weight basis), respectively. The color values of CBM and OFM were E 1cm 1% 205 nm = 60.24 and E 1cm 1% 278 nm = 65.21, respectively. CBM and OFM were found to be scarcely soluble in water and most common organic solvents, but soluble in alkaline aqueous and slightly soluble in DMSO. Both of them exhibited significant antioxidant activities superior to BHT. The reducing power/abilities of CBM and OFM increased with the amount of sample and decreased in the order of OFM > CBM > BHT. The metal chelating activities of CBM and OFM were concentration-dependent. Moreover, the metal scavenging effects of the samples decreased in the order of BHT > CBM > OFM. Results from the sun protection factor (SPF) in vitro determination of melanin-bearing gel formulations indicated that the SPF value of every formulation increased with amount of melanin, which suggested the presence of additional compounds with sunscreen activity in the melanin extract; the synergistic effect of CBM on the SPF of gel formulations was greater than that of OFM.

Studies on toxicity of antitubercular drugs namely isoniazid, rifampicin, and pyrazinamide in an in vitro model of HepG2 cell line

Abstract: Antitubercular drugs (ATT) are known to be majorly metabolized and detoxified in liver by both Phase I and Phase II group of drug metabolizing enzymes. These drugs as well as their metabolites are toxic and during this process cause injury to liver. In this study, we have investigated the in vitro hepatotoxic potential of both individual as well as combination ATT drugs using an in vitro model of human hepatocellular carcinoma cell line (HepG2). The cells were treated with varied concentrations of ATT drugs namely isoniazid (INH), rifampicin (RIF), and pyrazinamide (PYZ) for different durations. Cytotoxicity assay using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide) as well as morphological analysis using phase contrast microscopy have shown that concentrations used were not cytotoxic. However, pre-treatment with sub-cytotoxic concentrations of INH and PYZ increased the toxicity with the same drugs. This report corroborates the clinical finding that long-term treatment as well combination drug therapy with ATT induces hepatotoxicity rather than individual drugs.

Antidiabetic and antidyslipidemic activities of Cuminum cyminum L. in validated animal models

Abstract: The ethanolic extract of seeds of Cuminum cyminum (C.c) was found to improve glucose tolerance to the tune of around 18.3% (P < 0.01) in normal rats and shows around 17.7% (P < 0.01) and 17.1% fall on blood glucose levels at 0–300 and 0–1440 min, respectively, on streptozotocin-induced diabetic rats at an oral dose of 250 mg/Kg body weight. The extract has also been found to improve around 26.7% (P < 0.01) glucose intolerance on 14th day post treatment in high fructose fed streptozotocin-induced diabetic rats. The extract was also found to have antidyslipidemic activity as evident by 21.04% (P < 0.01) decline in serum triglycerides, 22.7% (P < 0.01) decline in total serum cholesterol, and 16.9% of decline in serum LDL-C, respectively, along with 12.2% (P < 0.05) increase in serum HDL-C on high fat diet fed male Syrian golden hamster. The extract was also found inhibitory to eye lens aldose reductase (EC 1.1.1.21) with IC50 value of 7.07 μg/ml as compared to the standard AR inhibiting compound Quercetin which showed IC50 2.35 μg/ml. The extract was also found inhibitory to α-glucosidase with IC50 value of 100 μg/ml as compared to known drug Acarbose which showed IC50 of around 25 μg/ml.

Synthesis and antimicrobial activities of novel bisacridine-1,8-dione derivatives

Abstract: A series of bisacridine-1,8-dione derivatives were synthesized by one-pot reaction of aromatic dialdehydes, dimedone or cyclohexane-1,3-dione and primer aromatic amines in acetonitrile to utilizing Amberlyst-15 as a heterogeneous catalyst. The structures of compounds were characterized by FT-IR, NMR, and elemental analysis. Antimicrobial activities of these compounds were determined by using the disc diffusion method against to these gram-positive and gram-negative bacteria and yeast. The results were compared with reference discs.

Synthesis and antibacterial evaluation of series of novel tri-substituted- s -triazine derivatives

Abstract: Two novel series of s-triazine derivatives (6a–e and 7a–f) were synthesized with various aromatic and heterocyclic amines. The synthesized compounds were subsequently evaluated for their in vitro antibacterial activity against three gram-positive viz. Bacillus subtilis (NCIM-2063), Bacillus cereus (NCIM-2156), Staphylococcus aureus (NCIM-2079) and gram-negative bacteria viz. Pseudomonas aeruginosa (NCIM-2036), Escherichia coli (NCIM-2065) and Klebseilla pneumoniae (NCIM-2706) by the broth dilution method as recommended by the National Committee for Clinical Laboratory Standards (NCCLS) using streptomycin as reference standard. Structures of the synthesized compounds were elucidated on the basis of elemental analyses and spectral data.

Synthesis and biological evaluation of anti-inflammatory activity of 1,3 diphenyl propenone derivatives

Abstract: A series of five chalcone derivatives were synthesized by Claisen–Schmidt condensation of acetophenone with appropriately substituted benzaldehyde in the presence of aqueous alkali. The synthesized compounds were characterized by their IR, NMR, and Mass spectral data. These compounds have been subjected to anti-inflammatory screening using the carrageenan-induced rat hind paw edema model. Chalcone derivatives at dose 25 mg/kg by oral route inhibited significantly the formation of edema. Chalcone posses a highly electrophilic α,β-unsaturated carbonyl moiety showed better anti-inflammatory activity.

Synthesis of some imidazolyl-substituted 2-benzylidene indanone derivatives as potent aromatase inhibitors for breast cancer therapy

Abstract: The synthesis and aromatase inhibitory activity of a new series of 2-benzylidene indanones is presented The imidazolyl-substituted indanones displayed potent aromatase inhibitory activity The vanilloid-based derivative 2-[4-(3-imidazol-1-ylpropoxy)-3-methoxybenzylidene]-indan-1-one (26) exhibited maximum inhibition of human placental aromatase and was found to be 54 times more potent as compared to aminoglutethimide

Synthesis, characterization, antibiogram and DNA binding studies of novel Co(II), Ni(II), Cu(II), and Zn(II) complexes of Schiff base ligands with quinoline core

Abstract: A series of Co(II), Ni(II), Cu(II), and Zn(II) complexes of Schiff base ligands L1H3 and L2H have been prepared. The ligands are synthesized by the condensation of 2-hydroxy-3-formylquinoline with salicyloylhydrazide and 2-hydrazinobenzothiazole in absolute ethanol. The prepared complexes were characterized by the analytical and spectral techniques. The stoichiometry of the complexes is found to be 1:1. The presence of coordinated and lattice water is confirmed by the TG and DTA studies. Subsequently all the prepared complexes were screened for antimicrobial activity against bacteria and fungi. The Cu(II) complexes have been found to be more active than the ligand. In addition the DNA binding/cleaving capacity of the compounds was analyzed by absorption spectroscopy, viscosity measurement, thermal denaturation, and gel electrophoresis methods.

DNA cleavage and antimicrobial investigation of Co(II), Ni(II), and Cu(II) complexes with triazole Schiff bases: synthesis and spectral characterization

Abstract: The Co(II), Ni(II), and Cu(II) complexes with Schiff bases derived from 3-substituted-4-amino-5-mercapto-1,2,4-triazole and fluvastatin have been synthesized. Schiff bases exhibited thiol–thione tautomerism and coordinated to metal ion through azomethine nitrogen and thiolate sulphur atoms. Square planar geometry for all the metal complexes of the type ML2 has been proposed in the light of analytical, spectral (IR, UV–Vis., ESR, and FAB-mass), magnetic, and thermal studies. The antimicrobial studies of Schiff bases and their metal complexes against various antibacterial (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis) and antifungal (Aspergillus niger, and Pencillium Chrysogenum) species by Minimum Inhibitory Concentration method revealed that, the metal complexes possess more healing antibacterial activity than the Schiff bases. Co(II), Ni(II), and Cu(II) complexes cleave the DNA isolated from A. niger.

Synthesis, anticonvulsant and toxicity screening of thiazolyl–thiadiazole derivatives

Abstract: Various thiazole-substituted thiadiazole derivatives (7a–t) were designed and synthesized using substituted acetophenones and substituted anilines as starting materials. Thiazole and thiadiazole moieties being anticonvulsants were clubbed together to get the titled compounds and their in vivo anticonvulsant screening were performed by two most adopted seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). Three compounds 7i, 7l and 7n were found to be potent in both the screens with comparable ED50 and better TD50 values than some standard drugs. These compounds were also found to exert lesser toxic effects on liver.

Microwave-assisted synthesis of some new tetrazolo[1,5-a]quinoline-based benzimidazoles catalyzed by p-TsOH and investigation of their antimicrobial activity

Abstract: Keeping the objective to build up a new structural class of potent antimicrobials, a series of some new 4-Benzimidazol-2-yl tetrazolo[1,5-a]quinoline derivatives has been synthesized by reaction of tetrazolo[1,5-a]quinoline-4-carbaldehyde and o-phenylenediamine in the presence of an organocatalyst p-TsOH under the influence of microwave irradiation. The identity of all the compounds has been established by 1H NMR, 13C NMR, FTIR, and elemental analysis. The synthesized compounds were subjected to in vitro antimicrobial screening against a representative panel of pathogenic strains including three Gram-positive bacteria (Bacillus subtilis, Clostridium tetani, and Streptococcus pneumoniae) and three Gram-negative bacteria (Escherichia coli, Salmonella typhi, and Vibrio cholerae) as well as two fungal organisms (Aspergillus fumigatus and Candida albicans) by employing broth microdilution method. Of the compounds studied, compound 5e demonstrated significant activity against a Gram-positive bacteria Bacillus subtilis.

Synthesis and cytotoxicity of novel chrysin derivatives

Abstract: A series of chrysin derivatives 8a–8v were prepared and tested in vitro against HCT-116 (human colon cancer cell line), Hela (human cervical carcinoma cell line), DU-145 (human prostate cell line), K562 (human leukemia cell line), and SGC-7901 (human gastric cancer cell line). The chemical structures of these compounds were confirmed by means of MS, IR, 1H NMR, 13C NMR, and elemental analysis. Among these derivatives, 7-(2-(piperazin-1-yl)ethoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one, 8n, had the strongest activity against HCT-116, Hela, DU-145, K562, and SGC-7901 cells.Open image in new window .

A facile synthesis of some 3-cyano-1,4,6-trisubstituted-2(1H)-pyridinones and their biological evaluation as anticancer agents

Abstract: The synthesis of some new 3-cyano-1,4,6-trisubstituted-2(1H)-pyridinones supported with various pharmacophores and functionalities at positin-1 is described. The in vitro anticancer activity of 24 of the newly synthesized compounds was evaluated according to the protocol of the NCI in vitro disease-oriented human cells screening panel assay. The results revealed that five compounds 4a–c, 7b, and 12b were able to display moderate antitumor potential against some of the tested subpanel tumor cell lines at the GI50 and TGI levels, however, with marginal or no cytotoxic (LC50) activity. The obtained data suggested that better antitumor activity was linked to derivatives with either 4-bromophenyl or 3,4-dimethoxyphenyl moieties, together with a 1-methyl-1H-pyrrol-2-yl counter part at positions 6 and 4, respectively. Consequently, the 3-cyano-4-(1-methyl-1H-pyrrol-2-yl)-6-(4-bromophenyl or 3,4-dimethoxyphenyl)-2(1H)-pyridinones 4a and 4b, could be considered as the most active members identified in this investigation as evidenced from their relative higher growth inhibitory (GI50 (MG-MID) 77.6 and 67.6 μM, respectively) and cytostatic (TGI (MG-MID) 85.1 and 95.5 μM, respectively) activities, when compared with the substituted thiocarbamoyl analog 7b and the bicyclic [1,2,4]triazolo[3,4-a]pyridine derivative 12b.

Synthesis and anti-inflammatory evaluation of some pyrazolo[3,4- b ]pyridines

Abstract: Novel series of pyrazolo[3,4-b]pyridines with basic skeleton different from the known COX inhibitors were synthesized from 5-amino-1-[4-(aminosulfonyl)phenyl]-3-phenyl-1H-pyrazole, which in turn was prepared by the condensation of (4-sulfamoylphenyl)hydrazine with α-cyanoacetophenone. All the newly synthesized compounds were tested for their in vivo anti-inflammatory activity by carrageenan-induced rat paw edema assay. Some of the most potent compounds were evaluated in different COX and LOX assays. Some of the new compounds were found to possess moderate anti-inflammatory activity.

Comparative research of chemical constituents and bioactivities between petroleum ether extracts of the aerial part and the rhizome of Atractylodes macrocephala

Abstract: A new possible resource of antimicrobial and antineoplastic was discovered for the first time from the aerial part of Atractylodes macrocephala Koidz. which was commonly disposed as waste. A comparative analysis of the constituents from the petroleum ether extracts of the aerial part and the rhizome of A. macrocephala was investigated by gas chromatography–mass spectrometry (GC/MS). Total of 21 compounds of the aerial part and 31 compounds of the rhizome of A. macrocephala were determined. Although the extracts of the aerial part and the rhizome showed little chemical composition correlation, both of them demonstrated antimicrobial and antitumor activities. Furthermore, the aerial part showed better cytotoxic activities than the rhizome with CEM cell line of IC50 values being below 10 μg/ml. These results could indicate that fatty oils from the aerial part of A. macrocephala had great potential to be used as a source for natural medicines or health products.

Synthesis and evaluation of a series of aminocyanopyridines as antimicrobial agents

Abstract: With the aim of developing potential antimicrobials, a series of 2-amino-3-cyanopyridines incorporating both sulfur and oxygen as part of the heteroaromatic ring (methyl thiophene, methyl furan) and fused cycloalkane groups were synthesized and characterized by FTIR, 1H-NMR, 13C-NMR, and bases of elemental analysis. All synthesized compounds were evaluated for their in vitro antibacterial and antifungal activity. Antibacterial and antifungal activities of aminocyanopyridines against Pseudomonas aeruginosa ATCC 29212, Bacillus subtilis RSKK 244, Bacillus megaterium (clinical isolate), the gram-positive bacterium Micrococcus luteus NRRLB 4375, and the fungus Candida albicans ATCC 90028 were studied. The relationship between the functional-group variation and the biological activity of the evaluated compounds is discussed.

Synthesis and analgesic activity of new 1,3,4-oxadiazoles and 1,2,4-triazoles

Abstract: A series of new 1,3,4-oxadiazoles and 1,2,4-triazoles were synthesized in order to obtain new compounds with potential analgesic activity. Compounds were evaluated for their analgesic activities by formalin-induced nociception test. Mefenamic acid (as the reference drug) did not show any activity in the early phase of the formalin test, while compounds 7b, 7c, 8c, and 9a significantly reduced the nociception in this phase. However in the late phase of formalin test all of the target compounds and mefenamic acid showed analgesic activity in comparison to control.

Design, synthesis, and anticonvulsant activity of novel quinazolinone analogues

Abstract: A number of 2-substituted and 2,3-disubstituted quinazolinone analogues have been synthesized. Their structures have been elucidated on the basis of elemental analyses and spectroscopic studies (IR, 1H NMR, and MS). An evaluation of the anticonvulsant activity of the prepared compounds has indicated that some of them exhibit moderate to significant activity, compared to diazepam and phenobarbital standards.

RP-HPLC method for the quantitative determination of fexofenadine hydrochloride in coated tablets and human serum

Abstract: Fexofenadine is a non-sedative and selective peripheral H1 receptor antagonist prescribed for allergic rhinitis and chronic urticaria. This article deals with a simple, feasible, and sensitive isocratic reverse-phase high-performance liquid chromatographic method for the determination of fexofenadine hydrochloride in bulk drug, pharmaceutical dosage forms and in human serum. The chromatography was carried out at 20 ± 2°C using two different chromatographs and five different stationary phases. The isocratic mobile phase was phosphate buffer pH 7.4 and methanol (methanol–phosphate buffer, 35:65, v/v), detection was made at 218 nm and the mobile phase flowed at 1 ml min−1. Validation parameters included linearity, accuracy, precision, specificity, limit of detection (LOD), limit of quantification (LOQ), and robustness over a linearity range 5–15 μg ml−1 according to the ICH guidelines (r > 0.9999), the inter- and intra-day precisions were relative standard deviation (RSD) 2.0, tailing factor ≤ 2.0, and theoretical plates > 2000). The retention time for five different stationary phases ranged from 3.78 to 4.15 min. The LOD and LOQ for the procedure were executed on samples containing very low concentrations of analytes on two different commercial brands of detectors.

Synthesis and preliminary evaluation of 2-substituted-1,3-benzoxazole and 3-[(3-substituted)propyl]-1,3-benzoxazol-2(3H)-one derivatives as potent anticancer agents

Abstract: The synthesis and cytotoxic activity studies of a new series of cyclic amine containing benzoxazole and benzoxazolone derivatives are described. The 2-cyclic amine-1,3-benzoxazoles 5a–k, 5-chloro-3-(3-chloropropyl)-1,3-benzoxazol-2(3H)-one 8 and 3-[3-(cyclic amino)propyl]-1,3-benzoxazol-2(3H)-ones 9a–f were synthesized. The newly synthesized compounds with the influence of the presence of cyclic amine moiety in the benzoxazole scaffold have been evaluated with respect to their cytotoxic effect toward four human cancer cell lines. The new compounds were evaluated to see whether substitution at the second and third position of the benzoxazole motif influence their cytotoxic effect toward cancer cells.

Synthesis, anti-HSV-1, and cytotoxic activities of some new pyrazole- and isoxazole-based heterocycles

Abstract: Ethyl 2,4-dioxo-4-(p-chloro)phenylbutyrate 2 obtained by condensation of 4-chloroacetophenone with diethyl oxalate was converted to 5-(4-chlorophenyl)-1-phenyl-1H-pyrazole-3-carbohydrazide 5 and 5-(4-chlorophenyl)isoxazole-3-carbohydrazide 6 in good yields. Treatment of 5 or 6 with phenylisothiocyanate and reaction of the resulting thiosemicarbazide 7 or 8 with chloroacetic acid and 4-fluorobenzaldehyde, phenacyl bromides gave the corresponding 4-thiazolidinone 9 or 10 or 1,3-thiazoles 11 or 12, respectively. While the intramolecular cyclization of 7 or 8 in concentrated sulfuric acid afforded 1,3,4-thiadiazoles 13 or 14. The reactivity of hydrazide 5 or 6 towards fluorinated aldehyde, hydrazonoyl chloride, and β-ketoester was studied to give fluorinated hydrazones, bis-hydrazones, and pyrazoles 15–23. The newly synthesized compounds were screened for their antiviral activity, and compound 19 reduced the number of viral plaques of Herpes simplex type-1 (HSV-1) by 69%. The detailed synthesis and spectroscopic and biological data are reported.