Screening of Anti-mycobacterial Phytochemical Compounds for Potential Inhibitors against Mycobacterium Tuberculosis Isocitrate Lyase
Background and Introduction: Tuberculosis (TB) is a leading infectious disease caused by Mycobacterium
tuberculosiswith high morbidity and mortality. Isocitrate lyase (MtbICL), a key enzyme of
glyoxylate pathway has been shown to be involved in mycobacterial persistence, is attractive drug target
against persistent tuberculosis.
Methods: Virtual screening, molecular docking and MD simulation study has been integrated for screening of
phytochemical based anti-mycobacterial compounds. Docking study of reported MtbICL inhibitors has shown
an average binding affinity score -7.30 Kcal/mol. In virtual screening, compounds exhibiting lower binding
energy than calculated average binding energy were selected as top hit compounds followed by calculation of
drug likeness property. Relationship between experimental IC50 value and calculated binding gibbs free energy
of reported inhibitors was also calculated through regression analysis to predict IC50 value of potential inhibitors.
Results: Docking and MD simulation studies of top hit compounds have identified shinjudilactone (quassinoid),
lecheronol A (pimarane) and caniojane (diterpene) as potential MtbICL inhibitors.
Conclusion: Phytochemical based anti-mycobacterial compound can further developed into effective drugs
against persistence tuberculosis with lesser toxicity and side effects.Journal Title:
Current Topics in Medicinal Chemistry