Azadiradione (AZD) neem biomass derived limonoid: extraction, characterization, and potential biological activities with special reference to anti-microbial and anti-cancer activities

Abstract

The resistance of conventional drugs to bacterial infections and cancer poses a significant threat to the healthcare system causing increased mortality. Metabolites derived from plant biomass mainly medicinal plants exhibit a wide spectrum of biological activities with high efficacy and biocompatibility. Given the rising importance of using natural compounds as an antimicrobial and anticancerous agent, the current study aimed to determine the antibacterial and anticancerous properties of Azadiradione (AZD), neem-derived limonoid. The antibacterial property of AZD was determined against two important nosocomial pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa and the anticancer activity of AZD was analysed through evaluation of cytotoxicity in human colon cancer cell line (HCT-116). The Minimum inhibitory concentration (MIC) of AZD was found to be ≥6.25 µM and ≥25 µM for S. aureus and P. aeruginosa, respectively. The fluorescent assisted cell sorter (FACS) and scanning electron microscope (SEM) analysis have also revealed that AZD (100 µM) exhibits effective antibacterial activity. The AZD has also exhibited cytotoxicity, inhibited cell migration, increased ROS generation and superoxide levels, reduces mitochondrial membrane potential (MMP), and induces apoptosis in a concentration-dependent manner (25 µM - 100 µM) in human colon cancer cell lines. The highest concentration (100 µM) of AZD was found to arrest the Sub G1 and G0/G1 phase of the cell cycle, upregulates mRNA expression of pro-apoptotic proteins such as Bax, caspase-3, caspase-9 and downregulate anti-apoptotic protein- Bcl-2. Thus, AZD could be regarded as an effective anticancer antibiotic in future therapeutics.