A discovery of potent kaempferol derivatives as multi-target medicines against diabetes as well as bacterial infections: an in silico approach

Abstract

Flavonoids demonstrate beneficial effects on human health because flavonoids contain important biological properties. Kaempferol is a flavonol, type of flavonoid found in eatable plants and in plants usually employed in ancient drugs (Moringa oleifera, Tilia spp., fern genus spp. and gingko etc.). Some medicinal studies have shown that the use of foods full of kaempferol decreases the risk of many (cancer, vascular) diseases. All the data of 50 kaempferol derivatives were collected from PubChem database. Through Schrödinger software, 3D-QSAR study was performed for 50 compounds by using method of field base. Conformer of kaempferol derivatives was docked against anti-diabetic, anti-microbial co-crystal structures and protein. To monitor the best anti-diabetic and antibacterial agent, particular kaempferol derivatives were downloaded from PubChem database. Virtual screening by molecular docking provided four lead compounds with four different proteins. These hit compounds were found to be potent inhibitor for diabetic enzymes alpha-amylase and DPP IV and had the potential to suppress DNA gyrase and dihydrofolate reductase synthesis. Molecular dynamic simulation of docked complexes evaluates the value of root mean square fluctuation by iMOD server. Kaempferol 3-O-alpha-L-(2, 3-di-Z-p-coumaroyl) rhamnoside (42) compound used as anti-diabetic and kaempferol 3-O-gentiobioside (3) as antibacterial with good results can be used for drug discovery.

Communicated by Ramaswamy H. Sarma

Keywords:

• Dihydrofolate reductase
• DNA gyrase
• kaempferol- 3-O-α-L-(2
• 3-di-Z-p-coumaroyl) rhamnoside
• 3D-QSAR
• DPPIV

Acknowledgments

The authors are thankful to Pakistan Science Foundation for providing technical and financial support to carry out the study. The authors extend their appreciation to the Researchers Supporting Project number (RSP2024R189), King Saud University, Riyadh, Saudi Arabia.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval

Not applicable.

Statement of human and animal rights

Not applicable.

Statement of informed consent

Not applicable.

Author contributions

Shagufta Parveen: Library preparation, drafting; Saman Shehzadi: molecular docking, validation of study; Maryam Rashid: proof reading, language check, figure quality and resolution; Nusrat Shafiq and Khalid S. Almaary: conceptualization, supervision, molecular docking study, funding; Sadaf Naz: proof reading, language check; Tahir Mehmood and Mohammed Bourhia: drafting, evaluation of results; Rabia Riaz and Hiba-Allah Nafidi: data analysis, literature.

Data availability Statement

Data will be available upon request from the corresponding author

Additional information

Funding

This study was supported by Pakistan Science Foundation under Research Grant CRP/PSF/TH-22. This work is funded by the Researchers Supporting Project number (RSP2024R189), King Saud University, Riyadh, Saudi Arabia.