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 7c , 7n , and 7h showed potential IC 50 values (9.8, 10, and 12 µM, respectively) which were comparable to erufosine IC 50 (9.8 µM) but lower potency than miltefosine IC 50 (3.5 µM). Preliminary assessment of cytotoxicity using human THP-1 cells presented chromone-peptidyl hybrids 7c and 7n as non-cytotoxic up to 100 µM while erufosine and miltefosine had CC 50 of 19.4 µM and >40 µM, respectively. In silico studies pinpointed the N - p -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 Ld CALP. Together, these findings present chromone-peptidyl hybrids 7c and 7n as potential and anticipated non-cytotoxic antileishmanial hit compounds for possible development of potential antileishmanial agents against visceral leishmaniasis.