Taofeek Saliu - Academia.edu (original) (raw)

Papers by Taofeek Saliu

Research Square (Research Square), Dec 10, 2023

Chloroquine resistance in Plasmodium falciparum, is the deadliest form of malaria. It is associat... more Chloroquine resistance in Plasmodium falciparum, is the deadliest form of malaria. It is associated with several mutations of PfCRT (P. falciparum chloroquine resistant transporter): PfCRT is a protein group that serves as a transporter in the parasite's digesting vacuole membrane. In the quest to battle chloroquine-resistant-P. falciparum strains, this study aim to predict the anti-plasmodial activity of ten (10) novel 4-aminoquinoline imidazole (4AQI) analogues (new-sets), whose activity was modeled using a multi-linear regression algorithm; trained by the structural-activity data from fteen (15) 4-aminoquinoline (4aq). Additionally, the study aim to understand the effect of electron delocalization and the extent to which the structural a nity of the new-sets has to the Pf3D7 protein. Results reveal that R 2 value (0.9180), R 2 pred value (0.8276), and Q 2 value (0.6672) obtained from the QSAR studies proofed to be su cient for constructing and testing the QSAR model. According to molecular docking studies, it was understood that new-sets with electron withdrawing groups, such as,-CO 2 H,-NO 2 ,-OH, F, Cl, and Br have a higher tendency toward plasmodium a nity than those with electron donating groups like-OCH 3 and-NH 2 against the Pf3D7 protein. All ten (10) 4AQI (new-sets) were approved as prospective drugs by the ADMET predictive study. Molecular dynamics results simulation at 50ns of time reveals that of all the new-sets, n16 and n21 stabilized the Pf3D7 (~ 0.1-0.2 Å) the most and better than chloroquine with respect to the protein structure. Furthermore, n16, n21, and chloroquine could provide exibility in two amino acid regions 180-230 (~ 0.95-1.55Å) and 260-289 (~ 0.7-1.2Å). Additionally, n16 and n21 complexes showed retained a stable range of 210-250 number of hydrogen bonds, while chloroquine maintained a range of 180-220 hydrogen bonds.

Research Square (Research Square), Dec 10, 2023

Chloroquine resistance in Plasmodium falciparum, is the deadliest form of malaria. It is associat... more Chloroquine resistance in Plasmodium falciparum, is the deadliest form of malaria. It is associated with several mutations of PfCRT (P. falciparum chloroquine resistant transporter): PfCRT is a protein group that serves as a transporter in the parasite's digesting vacuole membrane. In the quest to battle chloroquine-resistant-P. falciparum strains, this study aim to predict the anti-plasmodial activity of ten (10) novel 4-aminoquinoline imidazole (4AQI) analogues (new-sets), whose activity was modeled using a multi-linear regression algorithm; trained by the structural-activity data from fteen (15) 4-aminoquinoline (4aq). Additionally, the study aim to understand the effect of electron delocalization and the extent to which the structural a nity of the new-sets has to the Pf3D7 protein. Results reveal that R 2 value (0.9180), R 2 pred value (0.8276), and Q 2 value (0.6672) obtained from the QSAR studies proofed to be su cient for constructing and testing the QSAR model. According to molecular docking studies, it was understood that new-sets with electron withdrawing groups, such as,-CO 2 H,-NO 2 ,-OH, F, Cl, and Br have a higher tendency toward plasmodium a nity than those with electron donating groups like-OCH 3 and-NH 2 against the Pf3D7 protein. All ten (10) 4AQI (new-sets) were approved as prospective drugs by the ADMET predictive study. Molecular dynamics results simulation at 50ns of time reveals that of all the new-sets, n16 and n21 stabilized the Pf3D7 (~ 0.1-0.2 Å) the most and better than chloroquine with respect to the protein structure. Furthermore, n16, n21, and chloroquine could provide exibility in two amino acid regions 180-230 (~ 0.95-1.55Å) and 260-289 (~ 0.7-1.2Å). Additionally, n16 and n21 complexes showed retained a stable range of 210-250 number of hydrogen bonds, while chloroquine maintained a range of 180-220 hydrogen bonds.