Synthesis and evaluation of substituted 3-cinnamoyl-4-hydroxy-pyran-2-one (CHP) in pursuit of new potential antituberculosis agents.

Tuberculosis is an ever-evolving infectious disease that urgently needs new drugs. In the search for new antituberculosis agents, a library of 3-cinnamoyl-4-hydroxy-6-methyl-2-pyran-2-ones (CHPs) () was synthesized and evaluated against a standard virulent laboratory strain of H37Rv. Out of 25 compounds, , , and ( and ) showed least, moderate, good and appreciable activities, respectively, based on minimum inhibitory concentrations (MICs). Both and exhibited an MIC value of 4 μg ml, which was close to those of standard antituberculosis drugs ethambutol, streptomycin and levofloxacin. Neither nor showed any activity against Gram-positive or Gram-negative bacteria and even against non-tuberculous mycobacterium, . Thus, like the antituberculosis drugs rifampicin, isoniazid and pretomanid, they are highly TB specific. All the pyrone-based chalcones showed no recognizable level of cytotoxicity against normal human kidney cell line (HEK-293) up to 80 μM concentration and 11 exhibited an IC ≤ 100 μM (highest tested concentration). On further investigation, both and proved to be nontoxic against four human cell lines but proved to be a better choice as it did not reach IC even at 100 μM (highest tested concentration) while the IC of was around 80 μM. In conclusion, our results demonstrate that is specific against with no appreciable toxicity; its activity matches that of some clinically approved antituberculosis drugs and it therefore merits further evaluation.