RESUMEN
A dihydroartemisinin-ciprofloxacin hybrid was synthesized and its antiplasmodial activity was evaluated againstthe 3D7 strain of Plasmodium falciparum. It was hypothesized that linking the artemisinin pharmacophore (whichtargets the heme detoxification pathway of the malaria parasite) with the fluoroquinolone scaffold (which targetsplasmodial DNA gyrase enzyme) will produce a hybrid antimalarial compound with enhanced potency. The hybridwas synthesized by esterifying the carboxyl group of ciprofloxacin with the hydroxyl group of dihydroartemisinin; itdisplayed excellent antimalarial activity against the strain of P. falciparum tested with between 3- and 4-fold greateractivity (IC50: 2.99 nM) compared to the reference drugs chloroquine (IC50: 13.003 nM) and dihydroartemisinin alone(IC50: 9.968 nM) against the parasite. The synthesized compound was also tested for its in vitro cytotoxicity and itwas found to be relatively non-cytotoxic (LC50: 50.78 µg/ml) as compared to cyclophosphamide (LC50: 1.08 µg/ml). In silico prediction of the Lipinski properties of the hybrid showed that the compound possesses good drug-likeproperties. The hybrid demonstrated the good activity with minimal toxicity and is, therefore, a potential candidate forfurther exploration in the quest for desperately needed new antimalarial drugs.
RESUMEN
Acyclovir is a purine-based nucleoside antiviral agent used in the management of Herpes simplex and other viral infections. The present study is aimed at developing and validating a simple and rapid spectrophotometric method for its determination. The mechanism of the proposed method is based on the condensation/coupling reaction between Acyclovir and Ninhydrin-Ascorbic acid at pH 5. A purple colored product with maximum absorption at 540 nm was assayed to quantitatively evaluate the drug content in the formulation. The calibration curve was found to be linear up to 30 μg/ml. Analyte recovery tests carried out by the proposed method gave recovery of between 96.9 – 102.0%. Molar absorptivity and Sandells’ sensitivity were determined to be 41,071.43 L mol-1 cm-1 and 1.84 μg cm-2 respectively. The precision was assessed by determining the inter-day and intra-day variation which ranged between 1.45 – 1.63 % and 0.81 – 1.12 % respectively. The results show that the reaction produced a stable product and the proposed method is cost-effective and possesses adequate accuracy, precision and sensitivity. It can therefore be conveniently applied for the determination of acyclovir in dosage forms.