Discovery of new piperaquine hybrid analogs linked by triazolopyrimidine and pyrazolopyrimidine scaffolds with antiplasmodial and transmission blocking activities.

The World Health Organization (WHO) estimated that there were 247 million malaria cases in 2021 worldwide, representing an increase in 2 million cases compared to 2020. The urgent need for the development of new antimalarials is underscored by specific criteria, including the requirement of new modes of action that avoid cross-drug resistance, the ability to provide single-dose cures, and efficacy against both assexual and sexual blood stages. Motivated by the promising results obtained from our research group with [1,2,4]triazolo[1,5-a]pyrimidine and pyrazolo[1,5-a]pyrimidine derivatives, we selected these molecular scaffolds as the foundation for designing two new series of piperaquine analogs as potential antimalarial candidates.

Antimalarial and anti-inflammatory activities of new chloroquine and primaquine hybrids: Targeting the blockade of malaria parasite transmission.

Malaria is a disease that requires new drugs not only to fight Plasmodium but also to reduce symptoms of infection such as fever and inflammation. A series of 21 hybrid compounds were designed from chloroquine (CQ) and primaquine (PQ) linked to the pharmacophoric group present in phenylacetic anti-inflammatory drugs. These compounds were designed to have dual activity: namely, to be capable of killing Plasmodium and still act on the inflammatory process caused by malaria infection.

TP53 gene expression levels and tumor aggressiveness in canine mammary carcinomas.

The protein p53 is considered to be one of the most important tumor suppressor factors. Despite this importance, a potential association between TP53 messenger (m)RNA levels and tumor aggressiveness has not been well defined in animal cancer. We assessed and correlated TP53 gene expression in 40 canine mammary carcinomas with histologic grade, tumor size, and aggressiveness.

Different intra- and inter-molecular hydrogen-bonding patterns in (3,4a,8a)-2-[(2,3)-3-(2,5--benzamido)-2-(2,5--benzo-yloxy)-4-phenyl-butyl]---butyldeca-hydro-iso-quinoline-3-carboxamides ( = H or Cl): compounds with moderate aspartyl protease inhibition activity.

The crystal structures of (3,4a,8a)-2-[(2,3)-3-benzamido-2-benzo-yloxy-4-phenyl-but-yl]---butyldeca-hydro-iso-quinoline-3-carboxamide, CHNO, (I), and (3,4a,8a)-2-[(2,3)-3-(2,5-di-chloro-benzamido)-2-(2,5-di-chloro-benzo-yloxy)-4-phenyl-but-yl]---butyldeca-hydro-iso-quinoline-3-carboxamide, CHClNO, (II), are described. Despite their chemical similarity, they adopt different conformations in the solid state: (I) features a bifurcated intra-molecular N-H⋯(N,O) hydrogen bond from the -butylamide NH group to the piperidine N atom and the benzoate O atom, whereas (II) has an intra-molecular N-H⋯O link from the benzamide NH group to the -butyl-amide O atom. In the crystal of (I), mol-ecules are linked by (4) amide N-H⋯O hydrogen bonds into chains propagating in the [010] direction, with both donor and acceptor parts of the benzamide group.

Design, synthesis and anti-P. falciparum activity of pyrazolopyridine-sulfonamide derivatives.

Ten 1-phenyl-1H-pyrazolo[3,4-b]pyridine derivatives connected by a linker group to benzenesulfonamide moieties with different substituents in the 4-position were synthesized and assayed against Plasmodium falciparum. These ten compounds exhibited activity in vitro against the chloroquine-resistant clone W2 with IC50 values ranging from 3.46 to 9.

Anti-Plasmodium falciparum activity of quinoline-sulfonamide hybrids.

Fifteen quinoline-sulfonamide hybrids, with a 7-chloroquinoline moiety connected by a linker group to arylsulfonamide moieties with different substituents in the 4-position were synthesized and assayed against Plasmodium falciparum. The compounds displayed high schizonticidal blood activity in vitro, with IC50 values ranging from 0.05 to 1.

New compounds hybrids 1h-1,2,3-triazole-quinoline against Plasmodium falciparum.

Malaria is one of the most prevalent parasitic diseases in the world. The global importance of this disease, current vector control limitations, and the absence of an effective vaccine make the use of therapeutic antimalarial drugs the main strategy to control malaria. Chloroquine is a cost-effective antimalarial drug with a relatively robust safety profile, or therapeutic index.

[1-(3-Chloro-phen-yl)-1H-1,2,3-triazol-4-yl]methanol hemihydrate.

The asymmetric unit of the title hydrate, C(9)H(8)ClN(3)O·0.5H(2)O, comprises two independent 1,2,3-triazole mol-ecules and a water mol-ecule of crystallization. The dihedral angles between the six- and five-membered rings in the 1,2,3-triazole mol-ecules are 12.

Novel 1,2,3-triazole derivatives for use against Mycobacterium tuberculosis H37Rv (ATCC 27294) strain.

The purpose of this study was to prepare various 4-substituted N-phenyl-1,2,3-triazole derivatives using click chemistry. The derivatives were screened in vitro for antimicrobial activity against Mycobacterium tuberculosis strain H37Rv (ATCC 27294) using the Alamar Blue susceptibility test. The activity was expressed as the minimum inhibitory concentration (MIC) in μg/mL (μM).