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Literature DB >> 26487912

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

Kushalava Reddy Yempalla¹, Gurunadham Munagala¹, Samsher Singh¹, Gurleen Kour¹, Shweta Sharma¹, Reena Chib¹, Sunil Kumar¹, Priya Wazir¹, G D Singh¹, Sushil Raina¹, Sonali S Bharate¹, Inshad Ali Khan¹, Ram A Vishwakarma¹, Parvinder Pal Singh¹.

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.

Entities: Chemical Disease Species

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

Year: 2015 PMID： 26487912 PMCID： PMC4601052 DOI： 10.1021/acsmedchemlett.5b00202

Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345

19 in total

1. Synthesis and antituberculosis activity of a novel series of optically active 6-nitro-2,3-dihydroimidazo[2,1-b]oxazoles.

Authors: Hirofumi Sasaki; Yoshikazu Haraguchi; Motohiro Itotani; Hideaki Kuroda; Hiroyuki Hashizume; Tatsuo Tomishige; Masanori Kawasaki; Makoto Matsumoto; Makoto Komatsu; Hidetsugu Tsubouchi
Journal: J Med Chem Date: 2006-12-28 Impact factor: 7.446

Review 2. Targeting the formation of the cell wall core of M. tuberculosis.

Authors: Clifton E Barry; Dean C Crick; Michael R McNeil
Journal: Infect Disord Drug Targets Date: 2007-06

Review 3. Advances in the development of new tuberculosis drugs and treatment regimens.

Authors: Alimuddin Zumla; Payam Nahid; Stewart T Cole
Journal: Nat Rev Drug Discov Date: 2013-05 Impact factor: 84.694

Review 4. Delamanid: first global approval.

Authors: Nicola J Ryan; Jin Han Lo
Journal: Drugs Date: 2014-06 Impact factor: 9.546

5. In vitro and in vivo activities of the nitroimidazole TBA-354 against Mycobacterium tuberculosis.

Authors: A M Upton; S Cho; T J Yang; Y Kim; Y Wang; Y Lu; B Wang; J Xu; K Mdluli; Z Ma; S G Franzblau
Journal: Antimicrob Agents Chemother Date: 2014-10-20 Impact factor: 5.191

6. Synthesis and structure-activity relationships of varied ether linker analogues of the antitubercular drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5h-imidazo[2,1-b][1,3]oxazine (PA-824).

Authors: Andrew M Thompson; Hamish S Sutherland; Brian D Palmer; Iveta Kmentova; Adrian Blaser; Scott G Franzblau; Baojie Wan; Yuehong Wang; Zhenkun Ma; William A Denny
Journal: J Med Chem Date: 2011-09-01 Impact factor: 7.446

7. Synthesis and structure-activity relationships of antitubercular 2-nitroimidazooxazines bearing heterocyclic side chains.

Authors: Hamish S Sutherland; Adrian Blaser; Iveta Kmentova; Scott G Franzblau; Baojie Wan; Yuehong Wang; Zhenkun Ma; Brian D Palmer; William A Denny; Andrew M Thompson
Journal: J Med Chem Date: 2010-01-28 Impact factor: 7.446

8. Synthesis and structure-activity studies of biphenyl analogues of the tuberculosis drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824).

Authors: Brian D Palmer; Andrew M Thompson; Hamish S Sutherland; Adrian Blaser; Iveta Kmentova; Scott G Franzblau; Baojie Wan; Yuehong Wang; Zhenkun Ma; William A Denny
Journal: J Med Chem Date: 2010-01-14 Impact factor: 7.446

9. Structure-activity relationships of antitubercular nitroimidazoles. 2. Determinants of aerobic activity and quantitative structure-activity relationships.

Authors: Pilho Kim; Sunhee Kang; Helena I Boshoff; Jan Jiricek; Margaret Collins; Ramandeep Singh; Ujjini H Manjunatha; Pornwaratt Niyomrattanakit; Liang Zhang; Michael Goodwin; Thomas Dick; Thomas H Keller; Cynthia S Dowd; Clifton E Barry
Journal: J Med Chem Date: 2009-03-12 Impact factor: 7.446

10. OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice.

Authors: Makoto Matsumoto; Hiroyuki Hashizume; Tatsuo Tomishige; Masanori Kawasaki; Hidetsugu Tsubouchi; Hirofumi Sasaki; Yoshihiko Shimokawa; Makoto Komatsu
Journal: PLoS Med Date: 2006-11 Impact factor: 11.069

4 in total

Review 4. Recent Progress in the Discovery and Development of 2-Nitroimidazooxazines and 6-Nitroimidazooxazoles to Treat Tuberculosis and Neglected Tropical Diseases.

Authors: Hollis D Showalter
Journal: Molecules Date: 2020-09-10 Impact factor: 4.411