Click-based synthesis and antitubercular evaluation of novel dibenzo[b,d]thiophene-1,2,3-triazoles with piperidine, piperazine, morpholine and thiomorpholine appendages.
A series of novel piperidine, piperazine, morpholine and thiomorpholine appended dibenzo[b,d]thiophene-1,2,3-triazoles were designed and synthesized utilizing azide-alkyne click chemistry in the penultimate step. The required azide building block 6a-e was synthesized from commercial dibenzo[b,d]thiophene in good yields following five step reaction sequence. All the new analogues 8a-f, 9a-f, 10a-f, 11a-f &12a-f were characterized by their NMR and mass spectral analysis. Screening all thirty new compounds for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv, resulted 8a, 8f and 11e as potent analogues with MIC 0.78μg/mL, 0.78μg/mL & 1.56μg/mL, respectively, and has shown lower cytotoxicity. Interestingly, all six piperazine appended dibenzo[b,d]thiophene-1,2,3-triazoles 11a-f exhibited Mtb inhibition activity with MIC 1.56-12.5μg/mL. To some extent, the data observed here indicated Mycobacterium tuberculosis inhibition among the appendages is in the order, piperazine>thiomorpholine>morpholine.
Organic Chemistry Division-II (C P C Division), CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, Telangana, India.
Lokesh
L
Pulipati
Medicinal Chemistry and Antimycobacterial Research Laboratory, Pharmacy Group, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500078, Telangana, India.
Perumal
P
Yogeeswari
Medicinal Chemistry and Antimycobacterial Research Laboratory, Pharmacy Group, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500078, Telangana, India.
Dharmarajan
D
Sriram
Organic Chemistry Division-II (C P C Division), CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, Telangana, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, Telangana, India. Electronic address: kantevari@yahoo.com.
Srinivas
S
Kantevari
D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D057930:Click Chemistry; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D015394:Molecular Structure; D009025:Morpholines / Q000737:chemistry / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000995:Antitubercular Agents; D009025:Morpholines; D010879:Piperazines; D010880:Piperidines; D013876:Thiophenes; D014230:Triazoles; D000077489:Piperazine; C028971:thiamorpholine; C032727:piperidine; C037574:morpholine
Antitubercular agents; Click chemistry; Dibenzothiophene; Piperazine; Piperidine; Triazole