Title:Synthesis and Molecular Docking Studies of Glucose-linked Isonicotinoyl- 1,3,4-Thiadiazolidines as Antitubercular Agents
VOLUME: 15 ISSUE: 1
Author(s):Snehal A. Chavan*, Avinash G. Ulhe, Baliram N. Berad and Rupesh V. Chikhale
Affiliation:Department of Chemistry, Mahatma Jyotiba Phule Educational Campus, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, Department of Chemistry, Mahatma Jyotiba Phule Educational Campus, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, Department of Chemistry, Mahatma Jyotiba Phule Educational Campus, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) Tata Memorial Centre, Kharghar, Navi Mumbai
Keywords:1, 3, 4-Thiadiazolidines, antitubercular agents, glucopyranosyl isocyanodichloride, isonicotinoyl thiosemicarbazide,
M. tuberculosis H37Rv strain, isoniazid, molecular docking.
Abstract:Background: The recent emergence of multidrug-resistant strains of M. tuberculosis that are
resistant to two major effective drugs, viz. isoniazid and rifampicin, stimulated us to make an attempt
for the development of a new class of potent antitubercular agents by modifying the structures of existing
drugs. Aiming this, an efficient synthesis of glucose linked-isonicotinoyl-1,3,4-thiadiazolidines has
been carried out.
Method: The title compounds have been synthesized through cyclocondensation reaction of 1-
isonicotinoyl-4-aryl thiosemicarbazides with N-tetra-O-acetyl-β-D-glucopyranosyl isocyanodichloride.
The structures of newly synthesized compounds were verified by IR, 1H NMR, 13C NMR, mass spectrometry
and elemental analyses. The title compounds were evaluated for their in vitro antitubercular
potency against M. tuberculosis H37Rv strain using Lowenstein-Jensen method.
Results: A few title compounds were found to be equipotent with the reference drug rifampicin, while
moderately potent, when compared with the reference drug isoniazid. These compounds were subjected
to molecular docking studies and their results were found to be in agreement with the in vitro
studies.
Conclusion: We reported simple and efficient protocol for the synthesis of series of bioactive glucoselinked
isonicotinoyl-1,3,4-thiadiazolidines by utilizing N-tetra-O-acetyl-β-D-glucopyranosyl isocyanodichloride
as a suitable reagent for glycosylation. This approach is a valuable addition to the fastdeveloping
field of glucose-linked heterocycles and might be used to develop new potential drugs. We
demonstrated the introduction of isonicotinoyl and glucosyl moieties in single molecular framework
which may prove beneficial for developing new class of antitubercular agents.
