DESIGN, SYNTHESIS, ANTIMALARIAL EVALUATION AND COMPUTATIONAL STUDIES OF SOME CHALCONE DERIVATIVES
- Project Research
- 1-5 Chapters
- Abstract : Available
- Table of Content: Available
- Reference Style: APA
- Recommended for : Student Researchers
- NGN 3000
ABSTRACT
Inspired by the previous findings on the structural requirements needed for good antimalarial activity by chalcones against Plasmodium proteases, seventeen chalcone derivatives were designed and synthesized using Claisen-Schmidt condensation of appropriate aldehydes and methyl ketones. The structures of these compounds were established using various spectroscopic techniques. Based on SciFinder search the compounds; P1, P2, P3, and P8 are new compounds not listed on any chemical data base. The synthesized chalcones were screened in mice against established P. berghii infection. Eleven compounds were active and P2 the most active compound exhibited significant percentage inhibition of 90.32% (p˂0.05) at a dose of 100mg/kg. An interesting observation was the demonstration of good antimalarial activity with the 3-quinolinyl A ring derivatives- P3, P4 and P8. The potential of the synthesized compounds to inhibit the synthesis of β-hematin was also evaluated but, only compounds P12 and P17 showed modest inhibition of β-hematin synthesis with percent inhibition of 59.28% and 49.04% respectively at a dose of 50µg/kg. The prospects of dual inhibition of Plasmodium falciparum vital proteases; aspartic proteases (plasmepsin II and IV) and cysteine proteases (falcipain-2 and 3) of the seventeen chalcone derivatives was also investigated using insilico studies. Structure-based virtual screening using validated molecular docking revealed two potential hits (P3 and P4) with the best binding affinity and broad inhibition across all the proteases used. The crucial driving forces for receptor interaction and key interacting residues of the enzymes by the potential hits were established using molecular dynamics and binding free energy calculations. Simulation experiments revealed the xxv i stability of the docked ligands within all the enzymes. The ligands were found to interact with the residues at the active site and other sub-site regulating specificity for the falcipains system. With the plasmepsin systems, the ligands interact with the flap, covering the active site. From the different energetic contributions of the individual residues, it is evident that the binding process was principally favored by van der Waals and little affected by electrostatic energies while the polar solvation energy impaired it. With regard to the binding interactions, it appeared that the most contributing features of the ligands for receptor interactions are the quinoline ring, carbonyl group and 2- methoxy group. Therefore, the result from this work have identified quinolinyl chalcones with 2- methoxy substitution on ring B as potential candidates for further optimization as antimalarial against Plasmodium proteases.
Related Project Materials
EFFECTIVE PERSONAL SELLING STRATEGIES AND ITS IMPACTS ON THE MARKETING OF INDUSTRIAL PRODUCTS
BACKGROUND TO THE STUDY
Marketing has been defined differently by different scholar...
COUNSELLING TRAINING FOR COPING WITH STRESS IN COUNSELLING RELATIONSHIP
Background of the study
People all over the world experience one form of stress or the other irrespecti...
PHARMACOGNOSTIC AND ANTIBACTERIAL STUDIES OF THE LEAF EXTRACTS OF SWARTZIA MADAGASCARIENSIS DESV (FABACEAE)
ABSTRACT
This study evaluated the pharmacognostic standards and antibacterial properties of the leaf extracts of Swartzia madagascariensi...
BENEFITS OF EARLY CHILDHOOD EDUCATION ON GROSS MOTOR SKILLS
ABSTRACT: The benefits of early childhood education on gross motor skills...
PERCEPTION OF NORTHERN WOMEN IN YOLA METROPOLIS ON THE USE OF SEX APPEAL IN ADVERTISING
ABSTRACT
This study examines the perception of northern women on the use of sex appeal advertisements in Yola, the basis that underlined...
BUREAUCRACY AND EFFICIENCY IN ENUGU STATE CIVIL SERVICE
ABSTRACT
This research project is on Bureaucracy and efficiency (A case study of Enugu State civil service). It is...
INFLUENCE OF PEER GROUP ON THE ACADEMIC PERFORMANCE OF STUDENTS IN SOME SELECTED SECONDARY SCHOOLS IN OREDO LOCAL GOVERNMENT AREA OF EDO STATE
ABSTRACT
This study is designed to examiner and determine the effect of the activities of peer groups o...
EFFECTS OF GUIDED DISCOVERY AND THINK-PAIR SHARE METHODS ON ACADEMIC PERFORMANCE OF ECONOMICS STUDENTS IN COLLEGES OF EDUCATION
ABSTRACT
The study investigated the effects of guided discovery and think-pair-share method of teaching on academic performance in econom...
2023 NIGER REPUBLIC MILITARY TAKEOVER: FACT SHEET AND THE RESPONSE OF ECOWAS
Background of the study
The military takeover in Niger Republic in 2023 marks a significant episode in...
INFLUENCE OF INVENTORY MANAGEMENT ON FINANCIAL PERFORMANCE OF THE NIGERIAN MONEY DEPOSIT BANKS
Background to the Study
Inventory is a stock pile of products that a company offers for sale in various...
