Introduction: Introducing new and effective antitubercular agents is important in tuberculosis control programs. In this study, the in vitro antitubercular activity of two novel 1,4-dihydropyridine derivatives (F-27, Cl-33) were screened against a total of 113 different strains of Mycobacterium tuberculosis (77 susceptible and 36 resistant clinical isolates). Methodology: The in vitro activities of these compounds were evaluated based on the modified broth macro-dilution assay. Results: Compound F-27 showed more than 90% growth inhibition at the range of 2 to 8 μg/mL (minimum inhibitory concentration [MIC]90: 4.13 ± 0.45 µg/mL; p < 0.01), and complete growth inhibition was observed at the range of 8 to 32 μg/mL (minimum bactericidal concentration [MBC]: 11.2 ± 1.65 µg/mL; p < 0.01) against susceptible strains. However, 92% of the resistant strains showed some degree of susceptibility against this compound (MIC90 range: 16 to 64 µg/mL; mean: 40.4 ± 8 µg/mL; p < 0.01). It was found that although there is a linear relationship between the inhibitory activity of F-27 and isoniazid against resistant strains at low concentrations (r = 0.484, p < 0.001), there was no relationship between resistance to isoniazid and F-27 at higher concentrations (r = 0.019, p > 0.1). This may emphasize no cross-resistance between F-27 and isoniazid. Conclusions: Considering the sufficient sample size of the study and based on the excellent antimycobacterial activity of F-27, it could be concluded that F-27 is a potent candidate as a lead compound, and may be considered for development of a new antitubercular agent.

The game theory describes the interactions between two players and the pay-off from wining, losing or compromising. Mycobacterium tuberculosis ( Mtb) -host interactions were used as an example for the application of the game theory to describe and predict the possibilities of victory for any players. The gene expression for eight main markers of host response and three Mtb virulence factors were assessed in broncho-alveolar lavage of TB ⁺ and TB ⁻ patients. The game theory showed that a variety of paths exist that players can use, in response to the behaviour of the counterpart. Briefly, according to the “Nash equilibrium”, Ag85B is the main virulence factor for Mtb in active phase, however it is the most immunogenic factor if the host can respond by high expression of T-bet and iNOS. In this situation, Mtb can express high levels of ESAT-6 and CFP10 and change the game to the latency, in which host responses by medium expression of T-bet and iNOS and medium level of TGF-β and IDO. Consistently, The IDO expression was 134-times higher in TB ⁺ s than the TB ⁻ s, and the T-bet expression, ~200-times higher in the TB ⁻ s than the TB ⁺ s. Furthermore, Mtb -Ag85B had a strong positive association with CCR2, T-bet and iNOS, but had a negative correlation with IDO.