title: Synthesis and biological evaluation of new imidazo[2,1-b][1,3,4]thiadiazole-benzimidazole derivatives.
abstract: In this report, we describe the synthesis and biological evaluation of a new series of 2-(imidazo[2,1-b][1,3,4]thiadiazol-5-yl)-1H-benzimidazole derivatives (5a-ac). The molecules were analyzed by (1)H NMR, (13)C NMR, mass spectral and elemental data. The structure of one of the pre-final compounds, 6-(4-methoxyphenyl)-2-(4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde (4d) and that of a target compound, 2-[2-methyl-6-(4-methyl phenyl) imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-1H-benzimidazole (5aa) were confirmed by single crystal XRD studies. All the target compounds were screened for in vitro anti-tuberculosis activity against Mycobacterium tuberculosis H37Rv strain. Seven (5c, 5d, 5l, 5p, 5r, 5z and 5aa) out of twenty nine compounds showed potent anti-tubercular activity with a MIC of 3.125 μg/mL. A p-substituted phenyl group (p-tolyl or p-chlorophenyl) in the imidazo[2,1-b][1,3,4]thiadiazole ring and/or a chloro group in the benzimidazole ring enhance anti-tuberculosis activity whereas a nitro group in the benzimidazole ring reduces the activity. In the antibacterial screening, compounds 5i, 5w and 5ac showed promising activity against the tested bacterial strains. Further, antifungal and antioxidant activities of these molecules were also investigated. In the cytotoxicity study, the active antitubercular compounds exhibited very low toxicity against a normal cell line.
authors: Organic Chemistry Laboratory, Department of Chemistry, National Institute of Technology Karnataka, Surathkal, Srinivasanagar, Mangalore 575025, India.
authors: Jurupula
authors: J
authors: Ramprasad
authors: Organic Chemistry Laboratory, Department of Chemistry, National Institute of Technology Karnataka, Surathkal, Srinivasanagar, Mangalore 575025, India.
authors: Nagabhushana
authors: N
authors: Nayak
authors: Organic Chemistry Laboratory, Department of Chemistry, National Institute of Technology Karnataka, Surathkal, Srinivasanagar, Mangalore 575025, India. Electronic address: udayaravi80@gmail.com.
authors: Udayakumar
authors: U
authors: Dalimba
authors: Medicinal Chemistry and Drug Discovery Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Jawahar Nagar, Telangana 500078, India.
authors: Perumal
authors: P
authors: Yogeeswari
authors: Medicinal Chemistry and Drug Discovery Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Jawahar Nagar, Telangana 500078, India.
authors: Dharmarajan
authors: D
authors: Sriram
authors: Department of Biochemistry, Kuvempu University, Jnanasahyadri, Shankaraghatta 577451, India.
authors: S K
authors: SK
authors: Peethambar
authors: Department of Biochemistry, Kuvempu University, Jnanasahyadri, Shankaraghatta 577451, India.
authors: Rajeshwara
authors: R
authors: Achur
authors: Department of Bioinformatics, Kuvempu University, Jnanasahyadri, Shankaraghatta 577451, India.
authors: H S Santosh
authors: HS
authors: Kumar
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002470:Cell Survival; D002522:Chlorocebus aethiops; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology; D014709:Vero Cells
chemical_list: C000604353:2-(2-methyl-6-(4-methyl phenyl)imidazo(2,1-b)(1,3,4)thiadiazol-5-yl)-1H-benzimidazole; C000604352:5-chloro-2-(6-(4-fluorophenyl)-2-methylimidazo(2,1-b)(1,3,4)thiadiazol-5-yl)-1H-benzo(d)imidazole; D000935:Antifungal Agents; D000975:Antioxidants; D000995:Antitubercular Agents; D001562:Benzimidazoles; D013830:Thiadiazoles; C031000:benzimidazole
keywords: Antibacterial agent; Antioxidant activity; Benzimidazole; Cytotoxicity; Imidazo[2,1-b][1,3,4]thiadiazole; Mycobacterium tuberculosis