Author(s): Gupta Dheeraj Rajesh, Pankaj Kumar, Shriram Purohit, Abhishek Kumar, Kavita Apte

Email(s): pankajpgr@nitte.edu.in

DOI: 10.52711/0974-360X.2024.00411   

Address: Gupta Dheeraj Rajesh1, Pankaj Kumar1*, Shriram Purohit2, Abhishek Kumar1, Kavita Apte2
1Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Department of Pharmaceutical Chemistry, Mangalore, India.
2Department of Pharmaceutical Chemistry, SET’s College of Pharmacy, Dharwad, Karnataka, India.
*Corresponding Author

Published In:   Volume - 17,      Issue - 6,     Year - 2024


ABSTRACT:
Tuberculosis is one of the most common deaths in the developing world. According to the world health organization, it kills more than ten lakh people annually. Numerous drugs are available for treating tuberculosis, but challenges still exist due to resistance to the present drugs available. Keeping this in view, there is a need to develop a new antitubercular agent. In the present study, a series of benzimidazole thiadiazolyl azetidinone derivatives 5(a-h) were designed and synthesized using multiple steps. In the first step, using multiple steps, benzo imidazolyl acetate was prepared and converted to benzylidene benzo imidazolyl thiadiazol amine derivatives 4(a-h) intermediate. In the final step benzimidazole thiadiazolyl azetidinone derivatives 5(a-h) were prepared. All these synthesized compounds were confirmed using IR, 1H NMR, and mass spectral data. Further, the physiochemical properties of these compounds 5(a-h) and interaction pattern to receptor (PDB Code: 4COD) were studied using the Insilco method. Compounds 5(a-h) were evaluated for anti-tubercular activity against M. tuberculosis H37Rv using Microplate Alamar Blue Assay and compared with the standard drug isoniazid. Among all these compounds, 5b showed the best anti-tubercular activity with a MIC value of 3.12µg/ml. The docking score ranged from -2.13 to -5.07kcal/mol, and physiochemical properties were within prescribed limits. The anti-tubercular results of most compounds were promising, and among all compounds, 5b showed the best result, which can be further evaluated by in vivo studies.


Cite this article:
Gupta Dheeraj Rajesh, Pankaj Kumar, Shriram Purohit, Abhishek Kumar, Kavita Apte. In-silico ADME, Docking Studies, Synthesis of Thiadiazolyl benzimidazole linked Azetidinone derivatives as an Antitubercular agent. Research Journal of Pharmacy and Technology. 2024; 17(6):2628-2. doi: 10.52711/0974-360X.2024.00411

Cite(Electronic):
Gupta Dheeraj Rajesh, Pankaj Kumar, Shriram Purohit, Abhishek Kumar, Kavita Apte. In-silico ADME, Docking Studies, Synthesis of Thiadiazolyl benzimidazole linked Azetidinone derivatives as an Antitubercular agent. Research Journal of Pharmacy and Technology. 2024; 17(6):2628-2. doi: 10.52711/0974-360X.2024.00411   Available on: https://rjptonline.org/AbstractView.aspx?PID=2024-17-6-30


REFERENCES:
1.    De Macedo MB, Kimmel R, Urankar D, Gazvoda M, Peixoto A, Cools F, Torfs E et al. Design, synthesis and antitubercular potency of 4-hydroxyquinolin-2(1H)-ones. Eur J Med Chem. 2017; 138: 491–500. http://dx.doi.org/10.1016/j.ejmech.2017.06.061
2.    Aslam B, Wang W, Arshad MI, Khurshid M, Muzammil S, Rasool MH, Nisar NA et al. Antibiotic resistance: a rundown of a global crisis. Infect Drug Resist. 2018; 11: 1645-58. http://dx.doi.org/10.2147/IDR.S173867
3.    Sabale P, Bhagwat D, Sabale V. Synthesis and Anti-Tubercular Activity of Substituted Phenylpyrazole having Benzimidazole Ring. Res J Pharm Technol. 2018; 11(8): 3599-3608. DOI: 10.5958/0974-360X.2018.00662.5
4.    Kore PS, Honmane PP, Barkade RP, Mohite SK, Magdum CS. Microwave Synthesis of Some Novel 2-Substituted and N-Substituted Benzimidazole Derivatives and its Antimicrobial Activity. Res J Pharm Technol. 2016; 9(8): 1161-65. DOI: 10.5958/0974-360X.2016.00221.3
5.    Dokuparthi SK, Naik BJ, Kumar KS, Saidulu A. Synthesis, Characterization and Biological Evaluation of Benzimidazole Derivatives as Potential Anxiolytics. Res. J. Pharm. Technol. 2018; 11(1): 221-26. DOI: 10.5958/0974-360X.2018.00041.0
6.    Kumar U, Narang R, Nayak SK, Singh SK, Gupta V. Benzimidazole: Structure Activity Relationship and Mechanism of Action as Antimicrobial Agent.. Res. J. Pharm. Technol. 2017; 10(7): 2400-14. DOI: 10.5958/0974-360X.2017.00425.5
7.    Palled MS, Bhat AR, Patel A. Synthesis of New Series of Benzimidazole Acetic Acid Derivatives Bearing Thiophene Moiety for Anti-Tubercular Activity. Res J Pharm Technol. 2015; 8(6): 674-78. DOI: 10.5958/0974-360X.2015.00106.7
8.    Singh AK, Khare E, Chauhan HS. Evaluation of Benzimidazole Derivatives by using Aldehydes. Res J Pharm Technol. 2014; 7(6): 677-85.
9.    Jaouad EH, Badr A, Adnane B, M’hammed A, Jamal T. Benzimidazoles and Pharmacological Activities: A Review. Res. J. Pharm. Technol. 2014; 7(4): 481-88.
10.    Vijabaskaran M, Senthilraja M, Babu G, Sajeer P. Synthesis and Evaluation of Schiff’s Bases and Their Azetidinone Derivatives for It’s Antibacterial Activity. Res J Pharm Technol. 2011; 4(3): 375-79.
11.    Reddyrajula R, Dalimba U. Quinoline-1,2,3-triazole Hybrids: Design and Synthesis through Click Reaction, Evaluation of Anti-Tubercular Activity, Molecular Docking and In Silico ADME Studies. Chemistry Select. 2019; 4(9): 2685–93. https://doi.org/10.1002/slct.201803946
12.    Saundane AR, Yarlakatti M, Walmik P, Katkarf V. Synthesis, antioxidant and antimicrobial evaluation of thiazolidinone, azetidinone encompassing indolylthienopyrimidines. J Chem Sci. 2012; 124(2): 469–81. https://doi.org/10.1007/s12039-011-0180-6
13.    Vinodkumar R, Vaidya SD, Kumar BVS, Bhise UN, Bhirud SB, Mashelkar UC. Synthesis, Antibacterial, Antiasthmatic and Antidiabetic Activities of Novel N-Substituted-2-(4-phenylethynyl-phenyl)-1H-benzimidazoles and N-Substituted 2(4-(4,4-Dimethyl-thiochroman-6-yl-ethynyl)-phenyl)-1H-benzimidazoles. Eur. J. Med. Chem. 2008; 43(5): 986-95. http://doi:10.1016/j.ejmech.2007.06.013
14.    Keri RS, Hosamani KM, Reddy HS, Shingalapur RV. Synthesis, in-vitro antimicrobial and cytotoxic studies of novel azetidinone derivatives. Arch Pharm (Weinheim). 2010; 343(4): 237–47. https://doi.org/10.1002/ardp.200900188
15.    Parish T, Stoker NG. Mycobacteria Protocols. Methods in Molecular Biology. 1998. http://doi:10.1007/978-1-4939-2450-9


Recomonded Articles:

Research Journal of Pharmacy and Technology (RJPT) is an international, peer-reviewed, multidisciplinary journal.... Read more >>>

RNI: CHHENG00387/33/1/2008-TC                     
DOI: 10.5958/0974-360X 

1.3
2021CiteScore
 
56th percentile
Powered by  Scopus


SCImago Journal & Country Rank


Recent Articles




Tags


Not Available