Anti-Mycobacterial and Synergistic Activity of Synthetic Acridine-9-Carboraldehyde and 9-Hydroxy-4-Methoxy Acridine Alkaloids against Clinical Isolates of Multidrug-Resistant Mycobacterium Tuberculosis

Author(s): Lydia Bunalema, Moses Ocan, Godfrey S. Bbosa, Aloysious Lubega, Hindum Lanyero, Immaculate T. Nahereza

Background: Tuberculosis treatment has become difficult due to development of strains that are resistant to both first and second-line anti-TB drugs. This calls for a continued development of new drugs with novel targets against multi and extensively drug-resistant strains of M. tuberculosis. The aims of the study were; i) to determine the antimycobacterial activity of two synthetic alkaloids i.e., acridine-9-carboraldehyde and 9-hydroxy-4-methoxy acridine on both susceptible and multidrug-resistant TB clinical isolates and ii) to determine interactions between the alkaloids and anti-TB drugs iii) to determine the toxicity profile of the most active alkaloid.

Methods: Resazurin reduction microplate assay (REMA) was used to determine the minimum inhibitory concentrations of acridine-9-carboral-dehyde and 9-hydroxy-4-methoxy acridine as well as their interactions with conventional anti-TB drugs ie isoniazid, rifampicin and ciprofloxacin.

Results: Acridine-9-carboraldehyde was active on both susceptible and multidrug-resistant strains of TB with minimum inhibitory concentrations of 0.238µg/mL and 0.108 µg/mL on the pan-sensitive and clinical susceptible strains and 0.157 µg/mL and 0.196 µg/mL on the rifampicin resistant and multidrug-resistant strains respectively. In addition, acridine-9-carboraldehyde was synergistic to both rifampicin and levofloxacin with a fractional inhibitory concentration index of ≤ 0.5.

Conclusion: Acridine-9-carboraldehyde is active against clinical isolates of multidrug-resistant M. tuberculosis. And it is synergistic with rifampicin and levofloxacin on susceptible and multidrug-resistant M. tuberculosis.