Design, synthesis and biological evaluation of (E)-5-styryl-1,2,4-oxadiazoles as anti-tubercular agents.

Cinnamic acid and its derivatives are known for anti-tubercular activity. The present study reports the synthesis of cinnamic acid derivatives via bioisosteric replacement of terminal carboxylic acid with "oxadiazole". A series of cinnamic acid derivatives (styryl oxadiazoles) were designed and synthesized in good yields by reaction of substituted cinnamic acids (2, 15a-15s) with amidoximes. The synthesized styryl oxadiazoles were evaluated in vitro for anti-tubercular activity against Mycobacterium tuberculosis (Mtb) H37Ra strain. The structure-activity relationship (SAR) study has identified several compounds with mixed anti-tubercular profiles. The compound 32 displayed potent anti-tubercular activity (IC50 = 0.045 µg/mL). Molecular docking studies on mycobacterial enoyl-ACP reductase enzyme corroborated well with the experimental findings providing a platform for structure based hit-to-lead development.

1-[(2-Chloro-3-quinol-yl)meth-yl]indoline-2,3-dione.

In the title compound, C(18)H(11)ClN(2)O(2), the isatin and 2-chloro-3-methyl-quinoline units are both almost planar, with r.m.s. deviations of 0.0075 and 0.0086 Å, respectively, and the dihedral angle between the mean planes of the two units is 83.13 (7)°. In the crystal, a weak inter-molecular C-H⋯ O inter-action links the mol-ecules into chains along the c axis.

(2-Chloro-benzo[h]quinolin-3-yl)methanol.

In the title mol-ecule, C(14)H(10)ClNO, all non-H atoms are coplanar (r.m.s deviation = 0.0266 Å). In the crystal, symmetry-related mol-ecules are hydrogen bonded via inter-molecular O-H⋯O inter-actions, forming chains along the b axis.

2-Chloro-3-hydroxy-methyl-7,8-dimethyl-quinoline.

All non-H atoms of the title compound, C(12)H(12)ClNO, are co-planar (r.m.s. deviation = 0.055 Å). The hydr-oxy H atom is disordered over two positions of equal occupancy. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds, generating zigzag chains running along the b axis.

2-Chloro-3-hydroxy-methyl-6-methoxy-quinoline.

All the non-H atoms of the title compound, C(11)H(10)ClNO(2), are roughly coplanar (r.m.s. deviation = 0.058 Å). In the crystal, adjacent mol-ecules are linked by an O-H⋯N hydrogen bond, generating chains running along the a axis.