Studies of Antimicrobial Activities of some 4-Thiazolidinone Fused Pyrimidines, [1,5]-Benzodiazepines and their Oxygen Substituted Hydroxylamine Derivatives

Thiazolidin-4-one fused pyrimidines, [1,5]-benzodiazepines and their oxygen substituted hydroxylamine derivatives have been screened for antibacterial, antifungal and antimalarial activity. Bacillus subtilis, Escherichia coli, Proteus mirabilis and Salmonella typhi were used for antibacterial screening. Aspergillus fumigatus and Candida albicans were used for antifungal screening and Plasmodium species were used for antimalarial screening. The antibacterial and antifungal activities are expressed in terms of zone of inhibition and antimalarial activity is expressed in IC(50) value. Fifteen compounds 2Xa, 2Xb, 2Xc, 2Xs, 3IV, 3Va, 3Vc, 3VIIIa, 3VIIIh, 3IXa, 3IXb, 3IXc, 3Xa, 4IXa and 4Xa were tested for antibacterial as well as antifungal activity and seven compounds 2IXb, 2Xb, 3VIIIc, 3Xc, 4IXa, 4Xa and 4IXw were tested for antimalarial activity. Streptomycin, griseofulvin and chloroquine were taken as standard drugs in antibacterial, antifungal and antimalarial activity, respectively. The compound 2Xs was found significant antimicrobial against Bacillus subtilis, E. coli, Aspergillus fumigatus and Candida albicans as well as compound 3Xa was significant antimicrobial against Bacillus subtilis, E. coli, Salmonella typhi, Aspergillus fumigatus and Candida albicans. The compound 2Xb showed significant antimalarial activity.     

A novel group contribution method in the development of a QSAR for predicting the toxicity (Vibrio fischeri EC50) of ionic liquids

To achieve better management of processes and products, information on toxicity, safety, and risk assessment of chemicals is required. Ionic liquids are compounds of high interest for industry because of their attractive properties as solvents, but the water solubility of these compounds may lead to aquatic pollution and related risks. Experimental toxicity evaluation (Vibrio fischeri EC(50)) is a measurement of aquatic toxicity but there are theoretically over 1 million ionic liquids, which makes it necessary to estimate their properties by means of quantitative structure-activity relationships (QSARs). A database of Vibrio fischeri EC(50) was assembled to develop a novel group contribution method for estimating the EC(50) of ionic liquids. From the results the group contributions of anion, cation and alkyl substitutions has been calculated. The group contribution method allows an estimation of different combinations of groups in the toxicity (EC(50)) of ionic liquids.     

Synthesis, potent anti-staphylococcal activity and QSARs of some novel 2-anilinobenzazoles

Synthesis and anti-staphylococcal activity of a number of substituted 2-anilinobenzimidazoles, benzothiazoles and benzoxazoles are reported. The anti-staphylococcal activities were evaluated in standard in vitro MIC assay method. While anilinobenzimidazole derivatives 11-45 showed very potent anti-staphylococcal activities (greatest activity with an MIC value of 0.095 microg/mL), none of the 2-anilinobenzothiazoles and benzoxazole derivatives exhibited inhibitory activity. QSAR analysis of the anilinobenzimidazoles was studied on the relationship between the anti-staphylococcal activity (MIC in mug/ml) and extrapolated log k(w) values.     

QSAR analysis of 1,3-diaryl-4,5,6,7-tetrahydro-2H-isoindole derivatives as selective COX-2 inhibitors

Quantitative structure-activity relationship (QSAR) analysis was performed on a series of 1,3-diaryl-4,5,6,7-tetrahydro-2H-isoindole for their cyclooxygenase-2 (COX-2) inhibition. QSAR investigations were based on Hansch's extra thermodynamic multi-parameter approach and receptor surface analysis (RSA). QSAR investigations reveal that steric and electrostatic interactions are primarily responsible for COX-2 enzyme-ligand interaction. QSAR model derived from Hansch analysis demonstrated that COX-2 inhibitory activity is correlated with sum of atomic polarizability (Apol), number of hydrogen-bond donor groups (HBD), energy of the highest occupied molecular orbital (HOMO), desolvation free energy for water (F(H(2)O)) and fraction of areas of molecular shadow in the XY and ZX planes over area of enclosing rectangle (Sxyf and Sxzf) with r ranges 0.870-0.904. The best model was obtained from RSA model having r = 0.940 with good predictive ability (predicted compounds in training set and test set within +/- 1.0 unit of pIC(50)) and can be used in designing better selective COX-2 inhibitors among the congeners in future.     

QSAR for Predicting Joint Toxicity of Halogenated Benzenes to <Emphasis Type="Italic">Dicrateria zhanjiangensis</Emphasis>

In this study, the toxicity of 49 mixed halogenated benzenes to Dicrateria zhanjiangensis was determined and the partition coefficient of these mixtures was described by using the C₁₈-Empore^TM disks/water partition coefficient (K _mix). According to these data, a simple K _mix-based QSAR model was successfully used to correlate the toxicity of the mixed halogenated benzenes to D. zhanjiangensis.