IOSR Journal of Applied Chemistry (IOSR-JAC) e-ISSN: 2278-5736.Volume 11, Issue 7 Ver. II (July. 2018), PP 77-101 www.iosrjournals.org DOI: 10.9790/5736-11070277101 www.iosrjournals.org 77 |Page Synthesis and characterization of coumarin-4-thiazolidinone scaffolds as new class of anti-tuberculosis and antibacterial agents Jyoti M. Madar 1 , Lokesh A. Shastri 1* , Samundeeswari L. Shastri 1 , Megharaj Holiyachi 1 , Nirmala S. Naik 1 , Farzanabi Shaikh 1 , Vinay A. Sungar 2 , Shrinivas D. Joshi 3 . 1 Department of Chemistry, Karnatak University, Dharwad, Karnataka 580 003, India 2 Department of Chemistry, G.S.S. College, Belagavi, Karnataka 590006, India 3 Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S.E.T.’s College of Pharmacy, Sangolli Rayanna Nagar, Dharwad 580 002, Karnataka, India *Corresponding author: Lokesh A. Shastri Abstract: Our recent research target was to design biological active coumarin-4-thiazolidinone derivatives by using coumarin Schiff base which is pharmacologically and medicinally important scaffold. Synthesized novel coumarin-4-thiazolidinone derivatives were evaluated for their in vitro anti-tuberculosis activity against Mycobacterium tuberculosis strain H 37 Rv and showed moderate activity with MIC 25-100μg/mL. The antibacterial activity were also evaluated for synthesized compounds, among them compounds 5a and 5o showed the highest activity with MIC 1.6μg/mL and 0.8μg/mL respectively and these two are found to be more sensitive compounds against Gram positive bacterial strains S.aureus and B.subtilis. --------------------------------------------------------------------------------------------------------------------------------------- Date of Submission: 10-07-2018 Date of acceptance: 25-07-2018 --------------------------------------------------------------------------------------------------------------------------------------- I. Introduction Now a day’s science and technology has made implausible improvement in the field of medicine and developed various drugs against several diseases. Antibiotics are playing important role against infectious diseases and life threatening multi-drug resistant microorganisms 1 , Moreover, the continuous increase in antibiotic resistant strain has provoked the advance development of alternative bacterial infection therapies to keep control over microorganism resistance. Therefore, there is a requirement to design novel drug molecules with different mode of action 2,3 and most of the essential steps in research program are directed towards the development of new drugs 4 . Tuberculosis (TB) is one of the serious infectious diseases caused by microorganism bacillus mycobacterium tuberculosis 5 whereas; staphylococcus aureus is one more Gram positive bacteria, which is responsible for variety of infections 6 . Mycobacterium tuberculosis and S.aureus annoyed the species wall to infect the humans, thus these bacterial pathogens highlights the requirement for innovative class of drugs 7,8 . Heterocyclic compounds, especially nitrogen and sulfur containing small ring heterocycles have been under exploration for a long time due to their importance in medicinal chemistry 9 . Among all bioactive heterocyclic moieties, thiazolidinone analogs are taken unique place in drug design and discovery. 4- Thiazolidinone has been subjected to extensive study in the recent year, because it is core structure present in several biosynthetic and semi-synthetic products, for examples benzylpencillin, dicloxacillin and cloxacilin. Besides, 4-thiazolidinone having N-C-S linkage 10,11 showed antibacterial, antifungal 12 , anticancer 13 , anti- inflammatory, antiulcer, analgesic 14 antioxidant 15 , anti-tuberculosis, antiviral 16 and antileukaemic 17 activity so it is called as magic moiety due to its versatile biological activities 18 . Recent literature reported, 4-thiazolidinone is considered as good inhibitors of bacterial enzyme Mur B at micromolar level 19 . Natural penicillin and its related derivatives like sulbactam and tazobactam containing thiazolidine ring shows enormous biological activity 20 . On other hand oxygen containing coumarin heterocycles exhibited as interesting pharmacological properties 21 such as, antibacteria, antifungal 22 anti-inflammatory, antioxidant 23 , antiviral 24 , anticancer, anti- HIV 25 , antidiabetics 26 , and anti-tuberculosis 27 activity. It is also recognized that naturally occurring coumarin derivatives such as warfarin, mercumatilin, 677cumate, psoralen and calanolides are found to be pharmacologically and biologically active. While, novobiocin1 containing coumarin nucleus is strong DNA- gyrase inhibitors show terrific activity against Gram positive bacteria mainly S.aureus 28 . Whereas, (+)- calanolide A showed good anti-tubercular activity against all Mycobacterium tuberculosis strains and is the first compound to show anti-tuberculosis activity 29 . Thus, inspiring by anti-tubercular activity of calanolide, we were encouraged to design coumarin framework as anti-tubercular agents.
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Synthesis and characterization of coumarin-4 ...General experimental procedure for the synthesis of coumarin thiazolidine-4-one (5a-o). A mixture of coumarin Schiff base (3) (1 mmol)
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V. Conclusion Present research work is based on the discovery of novel antibacterial and anti-tuberculosis agent
coumarin thiazolidin-4-one using thioglycolic acid by sequential method. The anti-tuberculosis evaluation was
performed against all fifteen synthesized derivatives against Mycobacterium tuberculosis strain H37Rv, among
all compounds (5a-o) 5a, 5c and 5o are found to be moderately active with MIC 25μg/mL. Compounds 5a-o
exhibited a significant growth of inhibition against a wide spectrum of Gram positive bacterial strains.
Compounds 5a and 5o are found to be as more active and promising antibacterial agents against both Gram
positive bacterial strains S.aureus and B.subtilis with MIC 0.8-1.6μg/mL, whereas all other compounds showed
good activity with MIC ranging from 3.25 to 12.5μg/mL. It is interesting to note that, E.coli and P.aeruginosa
are most resistant towards our synthesized compounds and it is observed that, antibacterial activity result against
Gram positive bacterial strain shows a discrepancy to every compound based on different substitution group
present on both coumarin and aniline ring. Most of the compounds with methoxy and methyl group substitution
on coumarin and aniline ring showed good activity and more sensitive towards Gram positive bacterial strain.
Acknowledgment The authors are thankful to RGNF, UGC-UPE fellowship and DST for financial assistance to carry
research work. The author Jyoti M. Madar wish to offer deep gratitude to University of Sophisticated
Instrumentation Center (USIC) Karnatak University, Dharwad and NMR Research center, Indian Institute of
Science (IISC), Bangalore for providing necessary facility.
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