2. Academic Validation
  3. Synthesis and Biological Evaluation of Polar Functionalities Containing Nitrodihydroimidazooxazoles as Anti-TB Agents

Synthesis and Biological Evaluation of Polar Functionalities Containing Nitrodihydroimidazooxazoles as Anti-TB Agents

  • ACS Med Chem Lett. 2015 Sep 11;6(10):1059-64. doi: 10.1021/acsmedchemlett.5b00202.
Kushalava Reddy Yempalla 1,  Gurunadham Munagala 1,  Samsher Singh 1,  Gurleen Kour 1,  Shweta Sharma 1,  Reena Chib 1,  Sunil Kumar 1,  Priya Wazir 1,  G D Singh 1,  Sushil Raina 1,  Sonali S Bharate 1,  Inshad Ali Khan 1,  Ram A Vishwakarma 1,  Parvinder Pal Singh 1
Affiliations

Affiliation

  • 1 Medicinal Chemistry Division, Academy of Scientific and Innovative Research, Clinical Microbiology, PK-PD and Toxicology Division, and Preformulation Laboratory, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu 180 001, India.
PMID: 26487912 DOI: 10.1021/acsmedchemlett.5b00202
Abstract

Novel polar functionalities containing 6-nitro-2,3-dihydroimidazooxazole (NHIO) analogues were synthesized to produce a compound with enhanced solubility. Polar functionalities including sulfonyl, uridyl, and thiouridyl-bearing NHIO analogues were synthesized and evaluated against Mycobacterium tuberculosis (MTB) H37Rv. The aqueous solubility of compounds with MIC values ≤0.5 μg/mL were tested, and six compounds showed enhanced aqueous solubility. The best six compounds were further tested against resistant (Rif(R) and MDR) and dormant strains of MTB and tested for cytotoxicity in HepG2 cell line. Based on its overall in vitro characteristics and solubility profile, compound 6d was further shown to possess high microsomal stability, solubility under all tested biological conditions (PBS, SGF and SIF), and favorable oral in vivo pharmacokinetics and in vivo efficacy.

Keywords

6-nitro-2,3-dihydroimidazooxazole; MTB H37Rv; Mycobacterium tuberculosis; multidrug resistant-TB; structure−activity relationship.

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