No abstract

Malaria remains a febrile infection of public health concern in many countries especially tropical countries in Africa, and certain countries in Southern and North America such as Brazil, Costa Rica, Mexico, Dominican Republic, Colombia, and Ecuador. Hence this has made research into this area paramount. Acetophenones are active fragments in many compounds with promising antimalarial activity, such as chalcones. In this study, 3,5-diprenyl acetophenone (I) and 5-diprenyl (II) acetophenone were synthesized using an aromatic substitution reaction and tested for in-vivo antimalarial activity. The in-vivo antimalarial potential of the synthesized compounds was carried out using a curative model with plasmodium berghei infected mice. At all the three doses tested; 25 mgkg-1, 50 mgkg-1 and 100 mgkg-1 3,5-diprenyl acetophenone (I) showed promising activity with percentage inhibition of 68.03%, 65.16% and 69.75% respectively demonstrating dose-dependent activity. However, 5-prenyl acetophenone (II) only displayed significant activity (72.12% inhibition) at a dose of 100 mgkg-1. The two compounds passed Lipinski’s rule of five and thus drug-like candidates.

Malaria remain an epidermic infectious disease that is ravaging the world most especially sub-Sahara Africa. Due to the prevalence of Plasmodium parasites that are resistant to first-line antimalarial drugs, it is urgently necessary to create new scaffolds and find strategies to overcome drug resistance. Chalcones are well-known, uncomplicated analogs that may be easily produced using a variety of techniques and are widely present in natural products. Utilizing in silico tools, we developed new antimalarial agents from active synthetic and natural product fragments, and then we assessed their pharmacokinetics and pharmacodynamic profiles as therapeutic molecules against the biological targets of the parasite that causes the deadly type of malaria. In this research, active fragments from prenylated and quinolinyl chalcones with known antimalarial characteristics were combined via molecular hybridization. Four enzymes that have been implicated to the spread of malaria are used as the biological targets in the docking simulation for the ligands (prenylated-quinolinyl chalcone hybrids). Receptor-ligand complexes were viewed using Discovery Studio Visualizer 2017 and Chimera. Web-based tools (Moftsoft, SwissADME, Admetlab, and AdmetSAR 1 and 2) were utilized for drug-likeness and ADME prediction. The hybridized active segments created a brand-new scaffold with 169 new prenylated-quinolinyl chalcones. Post-docking studies found significant interactions between the drugs and the used targets. At least 25 of the compounds exhibit high affinities for the targets (-9.4 to -7.5 kcal/mol-1). The selected compounds had interesting ADME and drug-like properties. The compounds were qualified as possible antimalarial drugs due to their realistic pharmacokinetic and pharmacodynamic characteristics as well as their prospective antimalarial activity.

The goal of this research was to come up with novel antibacterial agents. Two hydrazones with a 2,4-dichloro moiety were synthesized by conventional synthetic methods with good yields. The success of the synthesis was confirmed by structure determination techniques; FITR and NMR analyses. The synthesized hydrazones were evaluated for antimicrobial activity using strains of bacterial and fungi. The two hydrazones demonstrated significant antibacterial and antifungal activities that were comparable to those of ciprofloxacin and fluconazole, respectively. Specifically, compound 3b with a para nitro group on its aniline fragment indicated a broader spectrum of activity compared to compound 3a. Additionally, the two hydrazones were active against bacterial strains such as Staphylococcus aureus, Campylobacter fetus, Proteus, mirabilis, and methicillin-resistant Staphylococcus aureus, which were resistant to ciprofloxacin with a ZI of between 25-31 mm and MIC of 12.5 μg/ml for Proteus mirabilis and 25 μg/ml for others, accordingly. Amazingly, the two hydrazones demonstrated bactericidal and fungicidal activity between 25 μg/ml and 100 μg/ml against all the sensitive bacterial and fungal strains. The two hydrazones with a 2,4-dichloro moiety have been identified as leads and are recommended for further in-vivo efficacy studies.

A solvent-free method for the synthesis of novel p-nitrophenyl hydrazones was successfully developed. The condensation of the p-nitrophenyl hydrazine with aromatic aldehydes through this mechanochemical technique furnished three products (3a-c) with moderate to high yield. The developed method is eco-friendly, efficient, simple, and convenient and indicated high reproducibility, short reaction time, catalyst-free, simple workup, and afforded pure and unsolvated products.