Malaria remains one of the prominent public health problems that lead to severe morbidity and mortality in many developing countries around the globe. New antimalarial drugs are urgently needed due to the emergence of antimalarial-resistant strains of Plasmodium falciparum. In previous studies, we tested several plants extracts that are capable of inhibiting β-hematin formation, with efficiency similar to chloroquine. In the current study, the effect of cinnamon ethanol and water extracts on inhibiting β-hematin formation was studied. Powdered cinnamon extracts and bark in a stick form were investigated using various extraction methods. A semi-quantitative in vitro method, based on the inhibition of ferriprotoporphyrin IX (FP) bio-crystallization developed by Deharo et al. (2002) was utilized. Water extracts of cinnamon revealed potential activity even at low concentration of infusions, which was manifested by a high capability to inhibit β-hematin formation in vitro.

Based on DFT, MP2, and the density functional from Truhlar group (hybrid GGA: MPW1k) calculations for an acid-catalyzed hydrolysis of nine Kirby's N-alkylmaleamic acids and two atenolol prodrugs were designed. The calculations demonstrated that the amide bond cleavage is due to intramolecular nucleophilic catalysis by the adjacent carboxylic acid group and the rate-limiting step is determined based on the nature of the amine leaving group. In addition, a linear correlation of the calculated and experimental rate values has drawn credible basis for designing atenolol prodrugs that are bitterless, are stable in neutral aqueous solutions, and have the potential to release the parent drug in a sustained release manner. For example, based on the calculated B3LYP/6-31 G (d,p) rates, the predicted t 1/2 (a time needed for 50% of the prodrug to be converted into drug) values for atenolol prodrugs ProD 1-ProD 2 at pH 2 were 65.3 hours (6.3 hours as calculated by GGA: MPW1K) and 11.8 minutes, respectively. In vitro kinetic study of atenolol prodrug ProD 1 demonstrated that the t 1/2 was largely affected by the pH of the medium. The determined t 1/2 values in 1N HCl, buffer pH 2, and buffer pH 5 were 2.53, 3.82, and 133 hours, respectively.

Biofilms, which consist of microorganisms embedded in a polymer-rich matrix, contribute to a variety of infections and increase antimicrobial resistance. Thus, there is a constant need to develop new chemotherapeutic agents to combat biofilms. This review article focuses on the use of alkyl gallates, gallic acid and its esters (methyl, ethyl, propyl, butyl, hexyl, octyl, and dodecyl gallate), most of which are found in plants, to inhibit biofilm formation. The studies under review reveal that alkyl gallates have the capacity to prevent biofilm development and eradicate mature biofilms through mechanisms that suppress the synthesis of the extracellular polymeric matrix, inhibit quorum-sensing signaling, and alter the microbial cell membrane. The effects are stronger the greater the length of the alkyl chain. Moreover, the alkyl gallates’ preventive activity against biofilm formation occurs at doses below the minimum inhibitory concentration. More importantly, combining alkyl gallates with antimicrobials or blue-light irradiation produces a synergistic effect on the inhibition of biofilm formation that can be used to treat infections and overcome microbial resistance.