Letters in Drug Design & Discovery - Volume 7, Issue 3, 2010

Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of ketolide derivatives as antibacterial agents. The 3D-QSAR models resulted from 42 molecules gave r2 cv values of 0.699 and 0.630, r2 values of 0.945 and 0.925. The predictive ability of CoMFA and CoMSIA, determined using a test set of 10 compounds, gave predictive correlation coefficients of 0.849 and 0.786, respectively. The results provided insight for predictive and diagnostic aspects of ketolide derivatives for better antibacterial activity.

Methicillin Resistant Staphylococcus aureus (MRSA) and Methicillin Sensitive Staphylococcus aureus (MSSA) are highly resistant to some antibiotics and it is difficult to treat infections caused by Staphylococcus aureus. This study evaluates the amount of Biofilm formation in four strains of MRSA and two strains of MSSA in presence of three antibiotics (mupirocin, tetracycline, and fusidic acid), two phytochemicals (epicatechin gallate and ethyl gallate) as single agents and in combination. Biofilm formation was quantified using spectrophotometry and visualized by Scanning Electron Microscope. Our results show that the combination of tetracycline with ethyl gallate, and tetracycline with epicatechin gallate were most effective in inhibiting the biofilm formation. It is interesting to observe that biofilm formation is inhibited significantly at synergistic concentration of combinations of antibiotics and phytochemicals. These results can be of potential therapeutic value towards development of new drugs for the prevention and treatment of infections caused by drug- resistant biofilm forming bacteria.

A series of N,N'-Bis(2-hydroxylbenzyl)-1,2-ethanediamine derivatives and its schiff bases were synthesized, characterized and screened for in vitro antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella enterica. Result indicated that the ethylenediamine derivatives, N,N'-Bis(2-hydroxy-5-bromobenzyl)-1,2- ethanediamine (21), and N,N'-Bis(2-hydroxy-5-chlorobenzyl)-1,2-ethanediamine (22) showed the most favorable antimicrobial activity exhibiting LC50 of 11.6 and 8.79 μM against S.enterica, 86 and 138 μM against P. aeruginosa, and 140 and 287 μM against S. aureus, respectively. These compounds displayed highest level of resistance with S. aureus. Thus, the high level of activity seen with the compounds (21, 22) suggests that these compounds could serve as the leads for development of novel synthetic compounds with enhanced antimicrobial activity.

A new series of 4-substituted 3H-1,2,3,5-oxathiadiazole 2-oxides bearing 1,2,3 triazole and piperidine ring has been synthesized in one step from amidoxime using thionyl chloride (SOCl2) and Triethylamine (TEA). All the synthesized compounds (10a-10l) are new and evaluated for their in vitro antifungal activities using standard agar plate method. SAR for the series has been developed by comparing their MIC values with miconazole and fluconazole. Compound 10j from the series was equipotent with miconazole against C. albicans and F. oxysporum whereas activity of compound 10i was comparable to miconazole against F. oxysporum and C.neoformans (MIC-30 μg/mL).

The synthesis of a series of andrographolide derivatives was described and their inhibitory effects on COX-2 expression in mouse macrophages were also evaluated. Some of the tested compounds showed better inhibitory potency than andrographolide, and compound (5d) was the best one.

We designed a novel recombinant fusion protein r-NAP5-hirudin 12-residue-RGD with bi-functional inhibitory activities against platelet aggregation and thrombin. Our strategy may supply a potential multi-functional drug for the prevention and management of thrombosis.

A series of N-aroylated isatins 1-15 was synthesized and evaluated for their antiglycation activity. All compounds showed a varying degree of glycation inhibitory activity with IC50 values between 18.01 ± 0.05-693.7 ± 3.0 μM, when compared with the standard (aminoguanidine) having an IC50 = 268.7 ± 12.4 μM. Compound 1 was found to be the most active member of this series with an IC50 = 18.01 ± 0.05 μM. Compound 10 showed an IC50 = 72.5 ± 0.09 μM, whereas compound 7 has an IC50 = 80.18 ± 0.07 μM. Compounds 3, 9, and 13 showed IC50 values 170.2 ± 0.62, 117.91 ± 2.9, 171.3 ± 0.79 μM, respectively. Rest of the compounds along with parent isatin were found to be inactive. The structures of all the synthetic compounds were deduced by spectroscopic analysis.

Comparative nucleophilicity of various α-nucleophiles like butane 2, 3-dione monoxime (BDMO), pralidoxime (2-PAM) and benzohydroxamic acid (BHA) towards hydrolysis of pesticide fenitrothion has been measured in the presence of various cationic surfactants at 27°C. It is shown that butane 2, 3-dione monoxime exhibits more reactivity for the degradation of fenitrothion. Effect of alkyl chain length, nucleophile concentration and pH on the rate of reaction of fenitrothion has also been studied.

A free web service (http://Cycloserver.organic.hu) was developed whereby cyclodextrin complexation of molecules can be estimated using molecular docking methodology. 98 various cyclodextrins were prepared in a dock-ready form on the server. Besides docking energy, the contact surface of the complex and dimerization energy of cyclodextrin hosts were calculated as well.

The synthesis and biological evaluation of a novel class of cannabinoid receptor agonists based on a 5- sulfonamide benzimidazole scaffold are reported. They showed a high binding affinity to both receptors with great in vivo potency. When given orally to rats, they produced a robust analgesia in different models of inflammatory and neuropathic pain.

A series of new 1,3-disubstituted-1H-pyrazol-5-ols (3) which are the analogues of known radical scavenger ‘edaravone’ are synthesized, characterized and evaluated for DPPH scavenging capacity. The docking studies are carried out for these compounds in the enol form and also in the respective keto form against the proteins and peptides involved in Alzhemier disease signal cascade. Some of them showed good radical scavenging capacity and molecular binding.

Umbilical cord blood (UCB) is widely considered as a potential alternative to bone marrow for haematopoietic stem cells. Efforts on UCB research have now taken a step further with the establishment of numerous cord blood banks throughout the world. Our aim is to improve the efficiency and end product of our bank because of the high running costs and administrative workload involved as well as finding a correlation between the reasons for rejecting UCB units (such as a low volume collected/ cell count) and obstetric factors. In 16 months we obtained 683 cord blood units by withdrawing residual blood from the placenta. The units were cryopreserved within 24 hours of extraction in a volume of at least 60mL with a nucleated cells total of 800 per 106. Analysis of the blood was also performed to exclude any bacterial contamination. However, 340 (49.75%) of the collected units were discarded. The main reasons were: low volume; low cell counts; patient/ family history; bacterial contamination; freezing problems; unit misidentification and no informed consent. Our study indicates that monitoring the reasons for rejecting UCB units on a regular basis could save the precious resources wasted on such units by identifying suitable units beforehand.