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One interesting approach to fight tuberculosis is the use of prodrugs that often have shown improved biological activities over drugs with poor absorption or difficulty to cross membranes. Previous studies demonstrate that weak acids such as benzoic acid, present antimycobacterial activity. Moreover, esters of those acids revealed to be a viable alternative since they may diffuse more easily through the cell membranes. Previously we showed that mycobacteria can easily activate benzoic acid esters by conversion to the corresponding acid. Since Zhang postulated that the activity of the acids can be dependent on their pKa, we set up to synthesize a library of benzoates with different electron withdrawing groups (4-chloro, 2,6-dichloro, 3,5-dichloro, 4-nitro, and 3,5 dinitro), to modulate pKa of the liberated acid and different alkoxy substituents (propyl, hexyl, and phenyl) to modulate their lipophilicity, and tested the activity of the esters and the corresponding free acids against mycobacteria. We also studied the activation of the esters by mycobacterial enzymes and the stability of the compounds in buffer and plasma. We concluded that all the benzoates in our study can be activated by mycobacterial enzymes and that the phenyl and hexyl esters presented higher activity than the corresponding free acids, with the nitrobenzoates, and especially the dinitrobenzoates, showing very interesting antitubercular activity that deserve further exploration. Our results did not show a correlation between the activity and the pKa of the acids.

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Snake venom has been the subject of numerous studies in an attempt to find properties and biological effects that may be beneficial to man. In this study we evaluated in vitro the effects of Crotalus durissus terrificus (Cdt) and Crotalus durissus collilineatus (Cdc) venom in human peripheral blood mononuclear cells (PBMCs). At 24 h, a significant decrease of viable cells was observed in cells stimulated with the Cdc venom at 0.0005 mg/mL and 0.005 mg/mL compared to the negative control. At 48 h, a significant decrease of viable cells was observed only in cells stimulated with Cdc venom at 0.005 mg/mL. A significant increase of TNF-α and IL-10 was detected 48 hours after culture of PBMC with Cdc, but not with Cdt venom. The expression of CD69 and PD1 (programmed death-1), activation and regulatory cell markers, on CD8+ and CD8− T cells did not change in the presence of Cdt and Cdc venom. Our results suggest the presence of proinflammatory and anti-inflammatory components in the Cdc venom. Further analysis should be done to identify those Cdc venom components as it has been done for the Cdt venom by other authors, indicating that modulatory components are found in the venom of different species of Crotalus snakes.

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Acetic acid-induced writhing, hot-plate, carrageenan-induced pleurisy, formalin-induced pain, croton oil-induced ear edema, vascular permeability tests and phospholipase A 2 activity assay were used to study the analgesic and/or antiinflammatory activity of the hydromethanolic fraction of ethanolic extract from Spiranthera odoratissima A. St.-Hil., Rutaceae, leaves (HMF) and its subfraction (sub-Fr 10-28 ). HMF and sub-Fr 10-28 reduced the leukocyte migration on the carrageenaninduced pleurisy test; sub-Fr 10-28 reduced the pain reaction time in the second phase of formalin-induced pain, as well as the ear edema and vascular permeability. Both HMF and sub-Fr 10-28 inhibited the phospholipase A 2 activity. These results suggest that the analgesic effect of this plant could be, in part, due to an anti-inflammatory action produced by the inhibition of phospholipase A 2 activity.

Snake venoms are recognized as a promising source of pharmacologically active substances and are potentially useful for the development of new antimicrobial drugs. This study aimed to investigate the antimicrobial activity of the venom from the rattlesnake Crotalus durissus terrificus against several bacteria. Antibacterial activity was determined by using the plate microdilution method and the activity on the bacterial envelope structure was screened by using the crystal violet assay. The proteins in crude venom were separated by electrophoresis and characterized regarding their proteolytic activity. C. d. terrificus venom exhibited antimicrobial action against gram-positive and gram-negative bacteria. MIC values were defined for Pseudomonas aeruginosa ATCC 27853 (62.5 µg/mL), Staphylococcus aureus ATCC 25923 (125 µg/mL), and Micrococcus luteus ATCC 9341 (≤500 µg/mL). For Salmonella enterica serovar typhimurium ATCC 14028 and Corynebacterium glutamicum ATCC 13032, the decrease in bacterial growth was not detected visually, but was statistically significant. The crystal violet assay demonstrated that the crude venom increased bacterial cell permeability and the secreted protein profile agreed with previous reports. The results suggest that the proteins with lytic activity against bacteria in C. d. terrificus venom deserve further characterization as they may offer reinforcements to the weak therapeutic arsenal used to fight microbial multidrug resistance.