In vitro activity of rhinacanthin analogues against drug resistant Plasmodium falciparum isolates from Northeast Thailand.

BACKGROUND: New anti-malarial drugs are needed urgently to address the increasing challenges of drug-resistant falciparum malaria. Two rhinacanthin analogues containing a naphthoquinone moiety resembling atovaquone showed promising in-vitro activity against a P. falciparum laboratory reference strain (K1). The anti-malarial activity of these 2 compounds was further evaluated for P. falciparum field isolates from an area of multi-drug resistance in Northeast Thailand. METHODS: Using a pLDH enzyme-linked immunosorbent assay, four P. falciparum isolates from Northeast Thailand in 2018 were tested for in vitro sensitivity to the two synthetic rhinacanthin analogues 1 and 2 as well as established anti-malarials. Mutations in the P. falciparum cytochrome b gene, a marker for atovaquone (ATQ) resistance, were genotyped in all four field isolates as well as 100 other clinical isolates from the same area using PCR-artificial Restriction Fragment Length Polymorphisms. Pfkelch13 mutations, a marker for artemisinin (ART) resistance, were also examined in all isolates. RESULTS: The 50% inhibitory concentrations (IC50) of P. falciparum field isolates for rhinacanthin analogue 1 was 321.9-791.1 nM (median = 403.1 nM). Parasites were more sensitive to analogue 2: IC50 48.6-63.3 nM (median = 52.2 nM). Similar results were obtained against P. falciparum reference laboratory strains 3D7 and W2. The ART-resistant IPC-5202 laboratory strain was more sensitive to these compounds with a median IC50 45.9 and 3.3 nM for rhinacanthin analogues 1 and 2, respectively. The ATQ-resistant C2B laboratory strain showed high-grade resistance towards both compounds (IC50 > 15,000 nM), and there was a strong positive correlation between the IC50 values for these compounds and ATQ (r = 0.83-0.97, P < 0.001). There were no P. falciparum cytochrome b mutations observed in the field isolates, indicating that P. falciparum isolates from this area remained ATQ-sensitive. Pfkelch13 mutations and the ring-stage survival assay confirmed that most isolates were resistant to ART. CONCLUSIONS: Two rhinacanthin analogues showed parasiticidal activity against multi-drug resistant P. falciparum isolates, although less potent than ATQ. Rhinacanthin analogue 2 was more potent than analogue 1, and can be a lead compound for further optimization as an anti-malarial in areas with multidrug resistance.

Dataset of 1H-nuclear magnetic resonance and mass spectra of surface modified Poly(amidoamine) dendrimers with LFC131 peptide.

In the present article, we describe the spectroscopic data of poly(amido)amine dendrimers generation 5.0 (G5 PAMAM) conjugated with LFC131 peptide at different specified reaction points. The raw data regarding the 1H NMR and mass spectra of G5 PAMAM dendrimers with and without LFC131 peptide conjugation and with or without FITC labelled are presented for comparison.

Targeted dendrimers for antagonizing the migration and viability of NALM-6 lymphoblastic leukemia cells.

Acute lymphoblastic leukemia (ALL) or white blood cell cancer is one of the major causes that kills many children worldwide. Although various therapeutic agents are available for ALL treatment, the new drug discovery and drug delivery system are needed to improve their effectiveness, to reduce the toxicity and side-effect, and to enhance their selectivity to target cancer cells. CXCR4 is a protein expressed on the surface of various types of cancer cell including ALL. In this work, the CXCR4-targeted PAMAM dendrimer was constructed by conjugating G5 PAMAM with a CXCR4 antagonist, LFC131. The results revealed that the LFC131-conjugated G5 PAMAM selectively targeted CXCR4 expressing leukemic precursor B cells (NALM-6) and the migration of NALM-6 cells induced by SDF-1α was inhibited at non-cytotoxic concentration. Further research based on this findings may contribute to potential anti-metastatic drugs for lymphoblastic leukemia.