Cinnamoyl-Oxaborole Amides: Synthesis and Their in Vitro Biological Activity

Abstract

Due to the increased interest in their application in the treatment of infectious diseases, boron-containing compounds have received a significant coverage in the literature. Herein, a small set of novel cinnamoly-oxaborole amides were synthesized and screened against nagana Trypanosoma brucei brucei for antitrypanosomal activity. Compound 5g emerged as a new hit with an in vitro IC50 value of 0.086 μM against T. b. brucei without obvious inhibitory activity against HeLa cell lines. The same series was also screened against other human pathogens, including Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), for which moderate to weak activity (10 to >125 μM) was observed. Similarly, these compounds exhibited moderate activity against the human protozoal pathogen Trichomonas vaginalis with no observed effect on common microbiome bacterial species. The cross-species inhibitory activity presents the possibility of these compounds serving as broad-spectrum antibiotics for these prevalent three human pathogens.

New Quinolone-Based Thiosemicarbazones Showing Activity Against Plasmodium falciparum and Mycobacterium tuberculosis

“…The starting compounds 7–10 were synthesized from the commercial accessible p -nitroacetophenone 6 as previously described in the literature [34]. Purity was determined by HPLC (Agilent, Santa Clara, CA, USA), and all compounds were confirmed to have purity >95% using a similar method previously described [35].…”

“…To assess antiplasmodial activity, three-fold serial dilutions of test compounds in culture medium were added to parasite cultures (adjusted to 2% parasitaemia, 1% haematocrit) in 96-well plates and incubated for 48 h. Duplicate wells per compound concentration were used. Parasite lactate dehydrogenase (pLDH) enzyme activity in the individual wells was determined as previously described [35,36].…”

Anti-Trypanosomal and Antimalarial Properties of Tetralone Derivatives and Structurally Related Benzocycloalkanones

“…The activity of the compounds against 427 Trypanosoma brucei brucei trypomastigotes was determined as previously described [37]. Briefly, parasites were incubated in 96-well plates with 20 µM or three-fold serial dilutions (100 µM starting concentration) of test compounds in Iscove’s modified Dulbecco’s medium (IMDM) (Lonza, Basel, Switzerland) supplemented with 10% fetal calf serum, HMI-9 supplement, hypoxanthine, and penicillin/streptomycin at 37 °C in a 5% CO 2 incubator.…”

Synthesis, Structure and In Vitro Anti-Trypanosomal Activity of Non-Toxic Arylpyrrole-Based Chalcone Derivatives

“…Further preliminary structure-activity relationship (SAR) investigations were conducted through Molecular hybridization, which combines two or more dissimilar pharmacophoric subunits to improve efficacy and other pharmaceutical profiles is becoming an attractive approach to design novel biologically active compounds [39][40][41]. Considering our ongoing research interests to identify and develop new antiparasitic compounds [42][43][44], we employed a molecular hybridization approach to design a target series of chalcone derivatives ( Figure 2) featuring A ring with hydroxyl and bromine substituents at position 2 and 5, respectively, and arylpyrrole containing B ring system. Herein, we wish to report the synthesis of a representative series of new and non-toxic arylpyrrole-based chalcone derivatives, along with their in vitro anti-trypanosomal effects against the nagana T. b. brucei strain.…”