Rational repurposing, synthesis, in vitro and in silico studies of chromone-peptidyl hybrids as potential agents against Leishmania donovani .

A chromone-peptidyl hybrids series was synthesised and rationally repurposed towards identification of potential antileishmanial hits against visceral leishmaniasis. Three hybrids , , and showed potential IC values (9.8, 10, and 12 µM, respectively) which were comparable to erufosine IC (9.8 µM) but lower potency than miltefosine IC (3.5 µM). Preliminary assessment of cytotoxicity using human THP-1 cells presented chromone-peptidyl hybrids and as non-cytotoxic up to 100 µM while erufosine and miltefosine had CC of 19.4 µM and >40 µM, respectively. studies pinpointed the --methoxyphenethyl substituent at the peptidyl moiety together with the oxygen-based substituted functions of the phenyl ring of the chromone moiety as crucial players in binding to CALP. Together, these findings present chromone-peptidyl hybrids and as potential and anticipated non-cytotoxic antileishmanial hit compounds for possible development of potential antileishmanial agents against visceral leishmaniasis.