Synthesis and Evaluation of Antileishmanial and Cytotoxic Activity of Benzothiopyrane Derivatives

Abstract

In continuation of our efforts to identify promising antileishmanial agents based on the chroman scaffold, we synthesized several substituted 2H-thiochroman derivatives, including thiochromenes, thichromanones and hydrazones substituted in C-2 or C-3 with carbonyl or carboxyl groups. Thirty-two compounds were thus obtained, characterized, and evaluated against intracellular amastigotes of Leishmania (V) panamensis. Twelve compounds were active, with EC50 values lower than 40 µM, but only four compounds displayed the highest antileishmanial activity, with EC50 values below 10 µM; these all compounds possess a good Selectivity Index > 2.6. Although two active compounds were thiochromenes, a clear structure-activity relationship was not detected since each active compound has a different substitution pattern.

Biological activities of 4H-thiochromen-4-one 1,1-dioxide derivatives against tropical disease parasites: A target-based drug design approach

“…The results of affinity energy bonding in all compounds are summarized in Fig. 8 , providing essential information about trends of interaction Ligand-TR; the green and violet boxes represent the scores of algorithms (Swiss dock and Autodock, respectively such as the reference ( R1–4 ) compounds, were considered as candidates for significant antileishmanial activity, previously reported [ 9 ], and R5 is the negative control due to low bioactivity [ 23 ]. This graph shows that series 6a–f presents a similar performance to that of R5 ; however, series 14a–d , 17a–b , and 21a–d present a similar or better affinity compared with the reference series ( R1–4 ).…”

Recent developments in thiochromene chemistry

“…Through these approaches, the group noted a common pathway that bifurcates into two distinct mechanisms depending on the substrate employed for the cyclization. The 39 Intriguingly, the product was formed as a diastereomeric mixture which, on dehydration or oxidation, resulted in thiochromenes (47 or 53) or a tautomeric keto-enol mixture (48 and 49), respectively (Scheme 12).…”

“…Ortiz et al (2020) exemplified this area of investigation by proposing a series of reactions based on the oxo-Michael aldol reaction of mercaptobenzaldehyde ( 45 ) with activated alkenes in the presence of 1,8-diazabicyclo-[5.4.0]-undec-7-ene (DBU) and triphenylphosphine (PPh 3 ). 39 Intriguingly, the product was formed as a diastereomeric mixture which, on dehydration or oxidation, resulted in thiochromenes ( 47 or 53 ) or a tautomeric keto–enol mixture ( 48 and 49 ), respectively (Scheme 12).…”