Prodiginines are a family of linear and cyclic oligopyrrole red-pigmented compounds possessing antibacterial,
anticancer and immunosuppressive activities and are produced by actinomycetes and other eubacteria. Recently,
prodiginines have been reported to possess potent in vitro as well as in vivo antimalarial activity against chloroquine
sensitive D6 and multi-drug resistant Dd2 strains of Plasmodium falciparum. In the present paper, a QSAR and
pharmacophore modeling for a series of natural and synthetic prodiginines was performed to find out structural features
which are crucial for antimalarial activity against these D6 and Dd2 Plasmodium strains. The study indicated that inertia
moment 2 length, Kier Chi6 (path) index, kappa 3 index and Wiener topological index plays important role in antimalarial
activity against D6 strain whereas descriptors inertia moment 2 length, ADME H-bond donors, VAMP polarization XX
component and VAMP quadpole XZ component play important role in antimalarial activity against Dd2 strain.
Furthermore, a five-point pharmacophore (ADHRR) model with one H-bond acceptor (A), one H-bond donor (D), one
hydrophobic group (H) and two aromatic rings (R) as pharmacophore features was developed for D6 strain by PHASE
module of Schrodinger suite. Similarly a six-point pharmacophore AADDRR was developed for Dd2 strain activity. All
developed QSAR models showed good correlation coefficient (r2 > 0.7), higher F value (F >20) and excellent predictive
power (Q2 > 0.6). Developed models will be highly useful for predicting antimalarial activity of new compounds and
could help in designing better molecules with enhanced antimalarial activity. Furthermore, calculated ADME properties
indicated drug-likeness of prodiginines.