Cholesterol-Based Conjugates: Synthesis, Characterization and In Vitro Biological Studies

Bacterial infections, malaria and cancer are causes of high death rates. Most of the drugs used to combat these diseases suffer from drug resistance, poor absorption and bioavailability and toxic side effects. Cholesterol is a sterol abundantly found in the human body and forms part of the structure and organisation of cell membranes. It is readily available, has functional groups that can be easily modified, and is affordable. In this research, different known therapeutic agents (anticancer, antimalarial and antibacterial) were conjugated to cholesterol and the synthesized compounds were characterized using FTIR, ¹H and ¹³C NMR, and Mass Spectroscopy, followed by in vitro antiplasmodial, antibacterial and anticancer studies. Thirteen compounds were successfully synthesized. Compound 10, containing curcumin and cholesterol was the most effective against all the Gram-positive strains of bacteria while compounds 9–11, containing either curcumin or zidovudine scaffold were effective against all the strains of bacteria. Compound 13, containing pyrimethamine and cholesterol showed good antiplasmodial activity with 97.75 and 97.83 % inhibition of asexual parasite proliferation at 20 and 10 μg/mL concentrations, respectively. In vitro cytotoxicity of the synthesized compounds on HeLa (cervical cancer) cells revealed IC₅₀ values for compounds 2 (7.559 μg/mL), 3 (5.840 μg/mL), 5 (1.44 mg/mL), 7 (4.308 μg/mL) and 11 (3.295 μg/mL) confirming promising anticancer activity.