Search

Synthesis of a variety of new 1-(isomeric fluorobenzoyl)-3-(isomeric fluorophenyl)thioureas ( 1a – t ) was accomplished in two steps. The synthetic route involves the reaction of equimolar quantities of isomeric fluorobenzoyl chlorides with potassium thiocyanate in anhydrous acetone to afford the corresponding isothiocyantes in situ, followed by treatment with equimolar quantities of isomeric fluoroanilines. All of the synthesized compounds ( 1a – t ) were screened for their in vitro antibacterial activity using Gram-positive bacteria ( Staphylococcus aureus , Bacillus subtilis ) and Gram-negative bacteria ( Escherichia coli , Pseudomonas aureginosa ). The minimum inhibitory concentration (MIC) was also determined for the most active compounds. In vitro antifungal activity was also determined against the five fungal species ( Rhizopus oryzae , Aspergillus tereus , Fusarium oxysporum , Aspergillus niger , Aspergillus fumigatus ). In general, the antifungal activity of compounds was better than their antibacterial activity.

Zinc monoglycerolate is used as a homogeneous catalyst in the transformation of 1,2- and higher order diols to yield cyclic carbonates or linear diurethane derivatives selectively in good yields.

Background: Approaches in disruption of MDM2-p53 interactions have now emerged as an important therapeutic strategy in resurrecting wild type p53 functional status. The present study highlights virtual screening strategies in identification of high affinity small molecule non-peptidic inhibitors. Nutlin3A and RG7112 belonging to compound class of Cis-imidazoline, MI219 of Spiro-oxindole class and Benzodiazepine derived TDP 665759 served as query small molecules for similarity search with a threshold of 95%. The query molecules and the similar molecules corresponding to each query were docked at the transactivation binding cleft of MDM2 protein. Aided by MolDock algorithm, high affinity compound against MDM2 was retrieved. Patch Dock supervised Protein-Protein interactions were established between MDM2 and ligand (query and similar) bound and free states of p53. Compounds with PubCid 68870345, 77819398, 71132874, and 11952782 respectively structurally similar to Nutlin3A, RG7112, Mi219 and TDP 665759 demonstrated higher affinity to MDM2 in comparison to their parent compounds. Evident from the protein-protein interaction studies, all the similar compounds except for 77819398 (similar to RG 7112) showed appreciable inhibitory potential. Of particular relevance, compound 68870345 akin to Nutlin 3A had highest inhibitory potential that respectively showed 1.3, 1.2, 1.16 and 1.26 folds higher inhibitory potential than Nutilin 3A, MI 219, RG 7112 and TDP 1665759. Compound 68870345 was further mapped for structure based pharamacophoric features. In the study, we report Cis-imidazoline derivative compound; Pubcid: 68870345 to have highest inhibitory potential in blocking MDM2-p53 interactions hitherto discovered.

Exploring healing power in plants emerged in prehistory of human civilization. Sustaining good health has been achieved over the millions of years by use of plant products in various traditional sockets. A major contribution of medicinal plants to health care systems is their limitless possession of bioactive components that stimulate explicit physiological actions. Luckily Pakistan is blessed with huge reservoir of plants with medicinal potential and some of them; we focused in this study for their medicinal importance.In this study we checked the antibacterial activity inherent in Ricinus communis, Solanum nigrum, Dodonaea viscose and Berberis lyceum extracts for multidrug resistance bacterial strains Klebsiella pneumonae, E. coli and methyciline resistant Staphylococcus aureus. MRSA showed sensitivity for Ricinus communis. Multidrug resistant Klebsiella pneumonae was sensitive with Pine roxburgii and Ricinus communis but weakly susceptible for Solanum nigrum. Multidrug resistant E. coli was resistant to all plant extracts. Treatment of severe infections caused by the bacterial strains used in this study with Ricinus communis, Pine roxburgii and Solanum nigrum can lower the undesired side effects of synthetic medicine and also reduce the economic burden.

Deferiprone is used as a chelation agent in chronic iron overload in β-thalassemia patients. Patients on deferiprone therapy show variable response to this drug in terms of reduction in iron overload as well as adverse drug reactions (ADRs). The pharmacogenetic studies on deferiprone have not carried out in patients with blood disorders in India. Therefore, the present study was carried out to evaluate the three most common nonsynonymous UGT1A6 polymorphisms Thr181Ala (541 A/G), Arg184Ser (552 A/C) and Ser7Ala (19 T/G) and therapeutic response to deferiprone in β-thalassemia major patients. Two hundred and eighty six (286) β-thalassemia major patients were involved in the study. Serum ferritin levels were estimated periodically to assess the status of the iron overload and the patients were grouped into responders and non-responders depending on the ferritin levels. The UGT1A6 2 polymorphisms were detected by PCR-RFLP methods. The association between the genotypes and outcome as well as ADRs was evaluated by Open EPI software. A significant difference was observed in the genotypic distribution of UGT1A6 2 Thr181Ala polymorphism in responders and non-responders. However, there was no difference in the genotypic distribution between patients with and without ADRs. As far as the UGT1A6 2 Arg184Ser polymorphism is concerned, no significant difference was observed between responders and non-responders. Further, evaluating the association of UGT1A6 2 Ser7Ala polymorphism with drug response, there was no significant difference in the genotypic distribution between responders and non-responders. However, there was a significant difference between responders with and without ADRs and non-responders with and without ADRs. In addition to this haplotype analysis was also carried out. However, we did not find any specific haplotype to be significantly associated with the deferiprone response in β-thalassemia major patients.

A series of 2-, 3-, and 4-substituted (fluorobenzoylimino)-3-aryl-4-methyl-1,3-thiazolines (2a–j) were synthesized in good yields by the base-catalyzed cyclization of corresponding 1-(fluorobenzoyl)-3-(fluorophenyl)thioureas (1a–j) with α-bromoacetone in water. Compared to the reactions in conventional nonaqueous solvents under inert anhydrous conditions, the aqueous medium provides a much cleaner, more efficient, and simpler method for synthesis.

The synthesis of several 2-(substituted fluorobenzoylimino)-3-(substituted fluorophenyl)-4-methyl-1,3-thiazolines ( 2a–t ) was carried out by base-catalyzed cyclization of corresponding 1-(fluorobenzoyl)-3-(fluorophenyl)thioureas ( 1a–t ) with 2-bromoacetone in aqueous medium. The structures of the synthesized compounds were confirmed by spectral and elemental analysis. All synthesized compounds were evaluated for in vitro antibacterial activity using Gram-positive bacteria ( Staphylococcus aureus , Bacillus subtilis ) and Gram-negative bacteria ( Escherichia coli , Pseudomonas aeruginosa ). The minimum inhibitory concentration (MIC) was determined for the most active compounds. In vitro antifungal activity was also determined against the five fungal species ( Rhizopus oryzae , Fusarium oxysporum , Aspergillus terreus , A. niger and A. fumigatus ).

The two m-methoxy groups of the title compound, C17H17FN2O4S, are almost coplanar with the aromatic ring [CH3—O—C—C = 5.8 (1) and 5.9 (1)°], whereas the methoxy group in the para position is bent out of the ring plane [78.6 (1)°]. Molecules are connected by intermolecular N—H...S hydrogen bonds to form centrosymmetric dimers that are stacked along the a axis.

In the title compound, C(7)H(7)FN(2)S, the aromatic ring plane and the thio-urea unit are twisted with a torsion angle C-C-N-C7 of 44.6 (2)°. In the crystal, N-H⋯S and N-H⋯F inter-molecular hydrogen bonds link the mol-ecules into infinite sheets that are stacked along the c axis.

Synthesis of a variety of new 1-(isomeric fluorobenzoyl)-3-(isomeric fluorophenyl)thioureas ( 1a – t ) was accomplished in two steps. The synthetic route involves the reaction of equimolar quantities of isomeric fluorobenzoyl chlorides with potassium thiocyanate in anhydrous acetone to afford the corresponding isothiocyantes in situ, followed by treatment with equimolar quantities of isomeric fluoroanilines. All of the synthesized compounds ( 1a – t ) were screened for their in vitro antibacterial activity using Gram-positive bacteria ( Staphylococcus aureus , Bacillus subtilis ) and Gram-negative bacteria ( Escherichia coli , Pseudomonas aureginosa ). The minimum inhibitory concentration (MIC) was also determined for the most active compounds. In vitro antifungal activity was also determined against the five fungal species ( Rhizopus oryzae , Aspergillus tereus , Fusarium oxysporum , Aspergillus niger , Aspergillus fumigatus ). In general, the antifungal activity of compounds was better than their antibacterial activity.

Background: Multiple blood transfusions are the mainstay of thalassemic patients in order to combat the severe anemia. These frequent blood transfusions result in the excessive iron deposition, leading to multiple injuries to a variety of organs in the body. In response to these injuries, the levels of various enzymes are disturbed. The whole phenomena usually involve the interrelation of one parameter with some other. The present study aimed to estimate the levels of serum ferritin and hepatic enzymes and to find out any possible correlation between them in thalassemic patients receiving multiple blood transfusions. Methods: A total number of 90 thalassemic patients of both sexes ranging from 10-15 years, receiving multiple blood transfusions were included in the present study. Blood samples from all the patients were withdrawn and analyzed for the values of serum ferritin, hemoglobin and hepatic enzymes (serum alanine transaminase, serum aspartate transaminase, serum alkaline phosphatase). Pearson correlation coefficient was applied to observe correlation between serum ferritin level and hepatic enzymes. A P value of ≤0.05 was considered statistically significant. Results: The overall values of serum ferritin, and hepatic enzymes (serum Alanine Transaminase, serum Aspartate Transaminase, serum Alkaline Phosphatase) were remarkably increased than their normal values. However, hemoglobin level was considerably decreased in thalassemic patients. A weak positive insignificant correlation was observed between serum ferritin with hepatic enzymes and hemoglobin in thalassemic patients. Conclusion: Multiple blood transfusions cause iron overload in the body, which in turn, lead to increased serum ferritin levels in thalassemic patients. High levels of hepatic enzymes are somewhat correlated to serum ferritin concentration. However, the exact reason of elevated levels is still unclear. Further detailed studies should be conducted in order to identify the exact mechanism behind this and to search for the promising correlations of various parameters in thalassemic patients receiving multiple blood transfusions.

Polymeric monoglycerolate complexes of zinc and cobalt can act as homogeneous catalysts for the one-pot synthesis of glycerol carbonate from glycerol and urea. Effects of reaction temperature, time and glycerol to urea molar ratios on glycerol carbonate selectivity and glycerol conversion have been analysed, with yields reaching 83% at 98% glycerol conversion. The proposed mechanism involves competing catalysed and uncatalysed pathways. In the catalysed pathway, an intermediate isocyanate complex, formed from reaction of urea with the metal monoglycerolate, undergoes rearrangement to form glycerol carbonate and ammonia.

In the title compound, C7H7FN2S, the aromatic ring plane and the thiourea unit are twisted with a torsion angle C—C—N—C7 of 44.6 (2)°. In the crystal, N—H...S and N—H...F intermolecular hydrogen bonds link the molecules into infinite sheets that are stacked along the c axis.