Optimization of Antimalarial Activity of Synthetic Prodiginines: QSAR, GUSAR, and CoMFA analyses

Abstract

In the present study, we have carried out extensive General Unrestricted Structure-Activity Relationships, conventional 3D-Quantitative Structure-Activity Relationships, and CoMFA analyses of synthetic prodiginines displaying moderate to high activities against Plasmodium Falciperum. 2D and 3D descriptors, various statistical parameters viz. R(2), R(2)(adj), standard error, Y-randomization, etc., were checked to build fruitful 3D-Quantitative Structure-Activity Relationships model. The best five parametric 3D-Quantitative Structure-Activity Relationships model is with R(2) = 0.924 and R(2)(pred) = 0.901. CoMFA was performed to check the electrostatic and steric regions, which affect the activity. The CoMFA model is graphically inferred using contour plots, which provide insight into the structural requirements for increasing the activity of a compound. The General Unrestricted Structure-Activity Relationships model, with R(2) = 0.940 and Q(2) = 0.912, suggests that the presence of F on aromatic ring is good for activity. The analyses reveal that lipophilicity plays a crucial role in deciding the activity for these molecules.

Optimization of antiproliferative activity of substituted phenyl 4-(2-oxoimidazolidin-1-yl) benzenesulfonates: QSAR and CoMFA analyses

“…It provides a useful alternative to animal testing, as well. CADD is a method of choice in drug designing process due to its faster, economical, and result oriented high success rate (Mahajan et al, 2012); (Mahajan et al, 2013); (Masand et al, 2012a); (Masand et al, 2013a); (Masand et al, 2012b); (Masand et al, 2013b). QSAR, molecular docking, pharmacophore modeling, etc.…”

“…QSAR, molecular docking, pharmacophore modeling, etc. are some of the successful brushwood of CADD that have led to the introduction of many drugs in the market ; ; (Mahajan et al, 2012); (Mahajan et al, 2013); (Masand et al, 2011); (Masand et al, 2012a); (Masand et al, 2010a); (Masand et al, 2010b); (Masand et al, 2013a); (Masand et al, 2012b); (Masand et al, 2013b) (see figure 2). …”

Determination of Optimum Values of Descriptors to Set Filters for Synthetic Tri-Pyrrole Derivatives (Prodiginines) Against Multi Drug Resistant Strain of <i>Plasmodium Falciparum</i>

“…Developing a potent antimalarial compound is still a major challenge for the medicinal chemists (Biamonte et al, 2013). The situation is worsening with the rapid spread of multi drug resistant strains of causative agent (Biamonte et al, 2013;Mahajan et al, 2012;2013;Mara et al, 2013;Masand et al, 2013b;Murugesan et al, 2013;Ojha and Roy, 2012;Papireddy et al, 2011). Therefore, there is essential need to curb this deadly disease either by modifying the existing marketed drugs or developing new therapeutic molecules.…”

“…Therefore, there is essential need to curb this deadly disease either by modifying the existing marketed drugs or developing new therapeutic molecules. Different compounds like xanthones, artemisinins, prodiginines have been synthesized and tested to develop new potential remedies for malaria (Biamonte et al, 2013;Mahajan et al, 2012;2013;Mara et al, 2013;Masand et al, 2013b;Murugesan et al, 2013;Ojha and Roy, 2012;Papireddy et al, 2011).…”

“…Prodiginines (Mahajan et al, 2012;2013;Masand et al, 2013b;Papireddy et al, 2011), the oligopyrrole derivatives with a characteristic conjugated system, are promising antimalarial agents (Fig. 1).…”