Synthesis of thymol-based pyrazolines: An effort to perceive novel potent-antimalarials.

A series of thymol based substituted pyrazolines and chalcones was synthesized and evaluated for antimalarial activity, using in-vitro and in-vivo malaria models. All the target compounds (5a-k and 6a-j) were found to be active against human malaria parasite strain Plasmodium falciparum NF54. Among all, compounds 5e and 5f of chalcone series and 6c and 6f of pyrazoline series exhibited prominent antimalarial activity with IC50 less than 3 and 2 µM respectively, while other pyrazolines also significantly inhibited the P. falciparum with IC50 less than 10 µM. The designed pharmacophores were found to be effective against P. falciparum. Compound 6f was found to be able to retard malaria progression in mice. This was evident through decreased parasitemia, increased mean survival time and hemoglobin content in the treated animals. Moreover, 6f was observed as an inhibitor of heme polymerization pathway of the malaria parasite. It also inhibited free heme degradation, which could be possibly responsible for higher reactive oxygen species (ROS) in parasite, thus inhibiting the rapid proliferation of the parasite. In addition to this, compound 6f was found to be non-toxic with a good selectivity index. Based on these observations, the compound 6f could be taken up for further antimalarial lead optimization studies.

Quebrachitol from Putranjiva roxburghii Wall. (Putranjivaceae) a potent antimalarial: Pre-clinical efficacy and its interaction with PfLDH.

Researchers are exploring natural resources in search of a new and effective anti-malarial compound to address the challenges in malarial treatment due to emerging incidences of drug-resistant strains. Following background knowledge of traditional medicine, we evaluated the in-vitro and in-vivo anti-malarial efficacy of Putranjiva P. roxburghii (Putranjivaceae) twigs ethanol extracts and fraction (PRT). In-vitro parasite-specific lactate dehydrogenase (pLDH) assay was performed using a chloroquine-sensitive Plasmodium falciparum strain. The results of the in-vitro study were further validated by in-vivo anti-malarial studies on P. berghei Keyberg 173 (K173) infected mice. The crude ethanol extract of the PRT showed the most moderate antiparasitic activity (IC50 = 15.51 µg/mL). In contrast, its butanol fraction extract showed potent activity (IC50 = 5.14 µg/mL) with a selectivity index (SI) of 28.87. Two phytochemicals, viz. 2, 4 dihydroxy-5-(hydroxymethyl) benzoic acid (DHMBA), and quebrachitol (QBC), were identified with anti-parasitic activity (IC50 = 5.01 µg/mL and 0.87 µg/mL) and selectivity index (SI) of 45 and 158. The in-vivo studies confirmed the significant anti-malarial activity of QBC at the dose of 30 and 60 mg/kg body weight with chemo-suppression values of 73.26% and 61.88%, respectively. The present study demonstrates the bioactive marker-based standardization of P. roxburghii twig, the antiplasmodial potential of PRT, and the role of QBC in suppressing parasitemia. The findings of the study support QBC as a prospective lead for a natural product-based adjunct remedy to conventional antiparasitic agents for malarial infectious.

Rosa damascena restrains Plasmodium falciparum progression in vitro and impedes malaria pathogenesis in murine model.

Malaria the parasitic disease of tropical countries is seeking newer therapeutic strategies owing to the drug resistance to existing drugs. The pathogenesis after infection renders the host to oxidative stress resulting in an altered immune status. Natural products rich in phenols are a source of bio-actives that could have a role in alleviating such condition. The present study reports the phenol rich ethyl acetate extract from the petals of Rosa damascena (RdEa) to be active against Plasmodium falciparum in-vitro and Plasmodium berghei in-vivo. It restores the haemoglobin level while increasing the mean survival time and chemo-suppression in P. berghei infected mice. The HPLC characterised RdEa was found to be rich in Gallic acid and Rutin besides other phenols. RdEa was capable of scavenging the free radicals and modulating the pro-inflammatory mediators (IL6, TNF, IFN and NO) favourably and also restored the architecture of hepatocytes as evidenced through histopathology. The extract was able to arrest the lipopolysaccharide (LPS) induced damage of J774A.1 cells (murine macrophages) and was found to be safe in mice upto 2000 mg/kg body weight.