The present study shown that the dihydrobenzimidazole thiopyranooxazinone derivatives were efficiently synthesized, which was further structurally elucidated by analytical as well as spectral studies. All these compounds screened for in vitro antimicrobial, antitubercular and anticancer activities. The result of antimicrobial activity revealed that the compounds having average to potent activity against Bacillus subtilis, Escherichia coli (antibacterial) and Aspergillus niger (antifungal) as compared to ciprofloxacin and fluconazole respectively. Compounds DPK3d1 exhibited potent antitubercular activities against Mycobacterium tuberculosis as compared to pyrazinamide, ciprofloxacin and streptomycin. Also, in cytotoxic studies compounds DPK3d3, DPK3d4 and DPK3d5 revealed that the potent activity against selected human cell line A459 as compared to Adriamycin.
Cite this article:
Deepak Kardile, Mrunal Shirsat. Synthesis and Evaluation of Antimicrobial, Antitubercular and Anticancer activities of Dihydrobenzimidazole thiopyranooxazinone derivatives. Research J. Pharm. and Tech 2021; 14(3):1453-1458. doi: 10.5958/0974-360X.2021.00259.6
1 Morse SS. Factors in the Emergence of Infectious Diseases. Emerging Infectious Disease.1995; 1:7-15.
2 Matsos A, Johnston IN. Chemotherapy-induced cognitive impairments: A systematic review of the animal literature. Neuroscience and Biobehavioral Reviews. 2019; 102: 382-399.
3 Saeed S, Rashid N, Jones PG, Ali M, Hussain R. Synthesis, characterization and biological evaluation of some thiourea derivatives bearing benzothiazole moiety as potential antimicrobial and anticancer agents. European Journal of Medicinal Chemistry. 2010; 45: 1323–1331.
4 Taramian S, Mahfoozi L, Soodm M. Antibiotic Resistance Trend of Uropathogens in a Tertiary Teaching Hospital in Rasht, Iran, a Longitudinal Study. International Journal of Pharmaceutical and Phytopharmacological Research. 2019; 9(1): 98-102.
5 Randhawa MA, Bawadekji A, Al Ali M, Oueslati MH, Jamith BW. Antimicrobial effects of methanolic extract of salvia officinal is l, including MRSA and multidrug resistant acinetobacter baumannii. International Journal of Pharmaceutical and Phytopharmacological Research. 2018; 8(4): 1-5.
6 Salehi NA, Motamedifar M. Antibiotic sensitivity profile of the bacterial isolates from the blood samples of the patients in different wards of a major referral hospital, shiraz, Iran. Pharmacophore. 2019; 10(2): 30-36.
7 Mohanty SK, Khuntia A, Yellasubbaiah N, Ayyanna C, Sudha BN, Harika MS. Design, synthesis of novel azo derivatives of benzimidazole as potent antibacterial and antitubercular agents. Beni-Suef University Journal of Basic and Applied Sciences. 2018; 7: 646-651.
8 Rashid M., Husain A. and Mishra R. Synthesis of benzimidazoles bearing oxadiazole nucleus as anticancer agents. European Journal of Medicinal Chemistry, 2013; 54: 855-866.
9 Seaton A.C., Mann J., Bailly C., Neidle S. and Berg H.V. Mechanistic and anti-proliferative studies of two novel, biologically active bis-benzimidazoles. European Journal of Cancer. 2003; 39: 2548–2555.
10 Gowda NR, Kavitha CV, Chiruvella KK, Joy O, Kanchugarakoppal SR, and Sathees CR. Synthesis and biological evaluation of novel 1-(4-methoxyphenethyl) 1Hbenzimidazole-5-carboxylic acid derivatives and their precursors as antileukemic agents. Bioorganic and Medicinal Chemistry Letters. 2009; 19: 4594-4600.
11 Knudson SE, Kumar K, Awasthi D, Ojima I, Slayden RA. In vitro-in vivo activity relationship of substituted benzimidazole cell division inhibitors with activity against Mycobacteria tuberculosis. Tuberculosis. 2014; 94 (3): 271-276.
12 Yoon YK, AliMA, Wei AC, Choon TS. Synthesis and evaluation of antimycobacterial activity of new benzimidazole aminoesters. European Journal of Medicinal Chemistry. 2015; 93:614-624.
13 Yajnanarayana HR, Miclmel AG, Joseph S. X-ray crystal structure and reactions of 2-cyano-1, 3-dibenzoyl-2, 3-dihydrobenzimidazole, a novel reissert compound. Tekahedmn Letters. 1991; 32:2997-3000.
14 Chen J, Qu J, Zhang Y, Chen Y, Liu N, Chen B. Metal-free construction of tricyclic or tetracyclic compounds-acid-promoted synthesis of benzo[4,5]imidazo[2,1-a]isoindole and1,2-dialkyl-2,3-dihydrobenzimidazoles.Tetrahedron. 2013;69:316-319.
15 Chen GF, Dong XY. Facile and Selective Synthesis of 2-Substituted Benzimidazoles Catalyzed by FeCl3/Al2O3. European Journal of Medicinal Chemistry. 2012; 9(1): 289-293.
16 Keri RS, Hiremathad A, Budagumpi S, Nagaraja BM. Comprehensive Review in Current Developments of Benzimidazole – Based Medicinal Chemistry. Chem Biol Drug Des. 2015; 86 (1):19-65.
17 Sridevi CH, Balaji K, Naidu A, Sudhakaran R. Synthesis of some phenylpyrazolo benzimidazolo quinoxaline derivatives as potent antihistaminic agents. European Journal of Medicinal Chemistry. 2010; 7: 234-238.
18 Ranjith PK, Rajeesh P, Haridas KR, Susanta NK, Row TN, Rishikesan R. Design and synthesis of positional isomers of 5 and 6-bromo-1-[(phenyl) sulfonyl]-2-[(4-nitrophenoxy) methyl]-1H-benzimidazoles aspossible antimicrobial and antitubercular agents. Bioorg Med Chem Lett. 2013; 23:5228–5234.
19 Arora RK, Kaur N, Bansal Y, Bansal G. Novel coumarin-benzimidazole derivatives as antioxidants and safer anti-inflammatory agents. Acta Pharm Sin B. 2014; 4: 368–375.
20 Pan T, He X, Chen B, Chen H, Geng G, Luo H. Development ofbenzimidazole derivatives to inhibit HIV-1 replication through protectingAPOBEC3G protein. European Journal of Medicinal Chemistry. 2015; 95: 500-513.
21 Vasantha K, Basavaraja swamy G, Rai MV, Boja P, Pai VR, Shruthi N. Rapid ‘one-pot’ synthesis of a novel benzimidazole-5-carboxylate and its hydrazone derivatives as potential anti-inflammatory and antimicrobial agents. Bioorg Med Chem Lett. 2015; 25: 1420-1426.
22 Gaba M, Gaba P, Uppal D, Dhingra N, Bahia MS, Silakari O. Benzimidazole derivatives: search for GI-friendly anti-inflammatory analgesic agents. Acta Pharm Sin B. 2015; 5:337-342.
23 Wen J, Luo Y, Zhang H, Zhao H, Zhou C, Cai G. A green and convenient approach toward benzimidazole derivatives and their antimicrobial activity. Chin Chem Lett. 2016; 27: 391–394.
24 Bansal Y, Silakari O. The therapeutic journey of Benzimidazoles: a review. Bioorganic and Medicinal Chemistry.2012; 20:6208-6236.
25 Haque RA, Budagumpi S, Choo SY, Choong MK, Lokesh BE, Sudesh K. Nitrile functionalized Hg (II) - and Ag (I)-N-heterocyclic carbene complexes: synthesis, crystal structures, nuclease and DNA binding activities. Appl Organometal Chem. 2012; 26: 689-700.
26 Ansari KF, Lal C. Synthesis physicochemical properties and antimicrobial activity of some new benzimidazole derivatives. European Journal of Medicinal Chemistry.2009; 44:4028-4033.
27 Gurrala S, Rajesh Y, Latha M. Symmetrical coupling of 2mercapto benzimidazole derivatives and their antimicrobial activity. Int J Pharm Sci,2011; 3 (2): 217-220.
28 Park SJ, Lee JC, Lee K. A Facile Synthesis of 4-Hydroxycoumarin and 4-Hydroxy-2-quinolone Derivatives. Bull Korean Chemical Society. 2007; 28 (7): 1203-1205.
29 Jogi PS. Synthesis, characterization and biological study of some new betti’s products International Journal of Researches in Biosciences, Agriculture and Technology. 2013; 1 (1):69-80.
30 Cappucino JG, Sherman N. Microbiology: a laboratory manual. California: Addison Wesley Longman Inc. 1999;263.
31 Isenberg HD. Clinical microbiology procedures handbook. American Society for Microbiology/ Washington DC. 1999;273.
32 Parish T, Stroker NG. Mycobacteria Protocols: Methods in molecular Biology. Totowa NJ: Humana Press Totowa. 1998; 101:395–422.
33 Kardile DP, Shirsat M. Synthesis and in vitro evaluation of coupled mercaptobenzimidazole derivatives used as a potent biological agent. International Journal of Pharmaceutical and Phytopharmacological Research. 2020; 10 (1): 127-133.
34 Collins LA, Franzblau SG. Microplate Alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium. Antimicrobial Agents Chemotherapy. 1997; 41:1004–1009.
35 Wang S. and Eisenberg D. 2003. Crystal structures of a pantothenate synthetase from M. tuberculosis and its complexes with substrates and a reaction intermediate. Protein Science. 2003;12:1097–10108.