A series of 1-[(4-benzyloxyphenyl)-but-3-enyl]-1H-azoles has been identified as potent antitubercular agents against Mycobacterium tuberculosis. Synthesis of compounds involved acid catalyzed ring-opening of cyclopropyl ring of phenyl cyclopropyl methanols followed by nucleophilic attack of the azoles on the carbocation intermediates. Several of the compounds 26, 34, and 36 exhibited significant antitubercular activities with MIC value as low as 1.56, 1.56, and 0.61 μg/ mL, respectively, comparable to many standard drugs. These compounds were also screened against other strains of bacteria and fungi, and few of them showed good antifungal activity against A. f umigatus, responsible for lung infection. KEYWORDS: Antitubercular agents, azoles, cyclopropyl methanols, Mycobacterium tuberculosis Mycobacterium tuberculosis (Mtb) causing tuberculosis is one of humanity's oldest and most resilient plagues, despite the availability of a four drug (INH, ethambutol, pyrazinamide, and rifampicin) regimen to treat the disease. 1 The long duration of therapy generally results in noncompliance of the treatment and results in multidrug resistance tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), which are highly lethal, extremely expensive and complicated to treat, posing new challenges for the prevention, treatment, and control of TB. 2−4 As per WHO, reported in 2011, about 8.7 million new cases of TB (13% coinfected with HIV) were reported with 1.4 million mortality. The latter include almost one million deaths among HIV-negative individuals and 430 000 among HIV-positive people. 5 Because of the drug−drug interactions, difficulty of the coadministration of anti-TB and anti-HIV drugs posed a new challenge before scientific community. 6 Despite the unraveling of mycobacterial genome sequence 7 and sound knowledge of mycobacterial biochemistry, none of the antitubercular drugs entered in the market for the last 50 years except a diraylquinoline (TMC 207) from Johnson & Johnson only very recently. 8,9 Unavailability of suitable vaccine and limitation of existing anti-TB drugs warrants the introduction of novel compounds or drug regimen effective against both the actively growing and latent stage mycobacterium avoiding drug−drug interactions.Azole and triazole based compounds are good as antifungal and antimycobacterial agents. 10 Such compounds generally inhibit cytochrome P450 (CYP121), an important enzyme with several of its isoforms of great significance in M. tuberculosis viability and pathogenicity. 11,12 Azoles also inhibit the biosynthesis of glycopeptidolipids (GPLs), an integral part of the mycobacterial cell envelope. 13 In an ongoing program for design and development of new antitubercular agents 14−17 we have identified phenyl cyclopropyl methanones and methanols as potent leads. 16,17 One of the phenyl cyclopropyl methanols (A) showed very good in vitro activity (MIC 3.12 μg/mL) against susceptible and drug resistant strains of M. Tuberculosis, and it exhibited marginal in vivo a...