N-Propargylated isatin-Mannich mono- and bis-adducts: Synthesis and preliminary analysis of in vitro activity against Tritrichomonas foetus

Abstract

Cu(I)Cl promoted synthesis of N-propargylated-isatin Mannich mono- and bis-adducts with an extension towards the synthesis of N-propargylated-isatin-7-chloroquinoline conjugates was described. The synthesized scaffolds were evaluated for their in vitro activity against the veterinary protozoal pathogen Tritrichomonas foetus and cytotoxicity against human prostate (PC-3) cancer cell line. The preliminary evaluation data revealed the enhancement in the activity profiles with the introduction of 7-chloroquinoline ring with the most active conjugates 7a, 7c and 7d exhibiting an IC₅₀ of 22.2, 11.3 and 24.5 μM respectively against T. foetus and minimal toxicity against human prostate (PC-3) cell lines.

Auranofin inactivates Trichomonas vaginalis thioredoxin reductase and is effective against trichomonads in vitro and in vivo

“…Trichomonas vaginalis strains G3, F1623 and S1469 [16] [or kindly provided by Dr Evan Secor, US Center for Disease Control and Prevention (CDC), Atlanta, GA] and Tritrichomonas foetus strains T-21, D1, C1 and C3 [17,18] were grown at 37 °C in TYM Diamond’s medium supplemented with 180 µM ferrous ammonium sulphate [19]. Drug susceptibility assays were performed as described previously [16].…”

Isatin dimers and their biological activities

“…[ 93 ] Replacement of the uracil linker by piperazine or 1,2,3‐triazole led to loss of activity, and dimers 39 (inhibitory rate: 3.0–71.2% at the concentration of 50 μM) and 40 (inhibitory rate: 44.23–57.61% at the concentration of 50 μM) were less active than the corresponding uracil‐containing compounds 38 , implying the uracil motif was crucial for the activity. [ 94–96 ] Among them, five dimers 38a–e with IC 50 values of 9.79–19.50 mM were found to be most active against T. vaginalis , and these dimers may represent novel scaffolds for the development of novel candidates for chemotherapy of human trichomoniasis.…”

Structural and biological survey of 7‐chloro‐4‐(piperazin‐1‐yl)quinoline and its derivatives

“…In 2014, Nisha et al synthesized compounds 40a‐c as N ‐propargylated‐isatin and 7‐chloro‐4‐(piperazin‐1‐yl)quinoline conjugates to be evaluated against Tritrichomonas foetus . The biological evaluation for 40a , 40b, and 40c showed activity with IC 50 of 22.2, 11.3, and 24.5 μM, respectively (Nisha, Bhargava, et al, 2014). Also, they identified compound 40b with great activity against Tritrichomonas vaginalis (IC 50 : 23 μM) (Nisha, Yang, et al, 2014).…”