Novel Diazenyl Containing Phenyl Styryl Ketone Derivatives As Antimicrobial Agents

Author(s): L. Sivasankerreddy*, B. Nagamani, T. Rajkumar, M.S. Babu, N.Y. Subbaiah, M.S. Harika, R. Nageswarao

Journal Name: Anti-Infective Agents
(Formerly Anti-Infective Agents in Medicinal Chemistry)

Volume 17 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Background: Antibiotics play an important role in the treatment of infections to the humans and at the same time, irrational, frequent prescription of higher antibiotics, change in gene composition of microorganisms are all the reasons behind the development and introduction of new antibiotics against different microorganisms.

Objective: In this project, an attempt has been made to synthesize some derivatives of diazenyl containing phenyl styryl ketones and also their in vitro screening was conducted against Mycobacterium tuberculosis, Escherichia coli, Klebsiella pneumonia, Bacillus subtilis, Staphylococcus aureus, Aspergillus niger and Candida albicans.

Methods: Ten molecules were synthesized which are diazenyl containing chalcones. 4- aminoacetophenone was diazotised and piperidine was coupled with the formed diazonium chloride. Further, the acetoxy group underwent Claisen-Schmidt condensation with differently substituted aldehydes to form the final compounds- the chalcones. The proposed chemical structures were confirmed by different spectroscopic techniques like FTIR, 1H NMR and Mass spectroscopy. TLC was used to know that the reactants were exhausted and the formation of the product occurred. Sharp melting point of the compounds concludes the purity.

Results: The MIC of the compounds 3CP, 3DP, 3EP and 3GP is 20 times the MIC of the standard fluconazole drug against Aspergillus niger. The compound 3GP is as equipotent as the standard drug Pyrazinamide with MIC of 3.12 µg/ml against Mycobacterium tuberculosis.

Conclusion: The results are quite promising which on further studies may lead to drug molecules against different microorganisms. Especially, 3EP can be considered as a broad spectrum agent due to its potent activity against different microorganisms like Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia and Candida albicans.

Keywords: Diazenyl styryl chalcones, antimicrobial, antifungal, piperidine, claisen-schmidt, pyrazinamide.

Life media centre. The burden of fungal disease. LIFE, 2017.(Avialable at:.
Barr, C.E. Oral diseases in HIV-1 infection. Dysphagia, 1992, 7(3), 126-137.
Rasika, S.B.; Mona, U.S.; Yogesh, S.D.; Vidhi, A.S.; Supriya, P.K. Antibacterial activity of curcumin (turtmeric) against periopathogens-An in vitro evaluation. J. Adv. Clin. Res. Insig., 2017, 4, 175-180.
Kaplan, J.E.; Benson, C.; Holmes, K.K.; Brooks, J.T.; Pau, A.; Masur, H. Centres for disease control and prevention. guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. recommendations from cdc, the national institutes of health and the HIV medicine association of the infectious diseases society of america. MMWR Morb. Mortal. Wkly. Rep., 2009, 58, 45-48.
Eggimann, P.; Garbino, J.; Pittet, D. Epidemiology of Candida species infections in critically ill non-immunosuppressed patients. Lancet Infect. Dis., 2003, 3(11), 685-702.
Marcus, B.; Ian, B.R. An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles. Beilstein J. Org. Chem., 2013, 9, 2265-2319.
Harmeet, K.; Siong, M.L.; Kalavathy, R.; Mani, V.; Syed, A.A.S.; Narasimhan, B.; Kaur, H. Diazenyl schiff bases: Synthesis, spectral analysis, antimicrobial studies and cytotoxic activity on human colorectal carcinoma cell line (HCT-116). Arabian. J. Chem., 2017. (In Press)
Jyotirmaya, S.; Sudhir Kumar, P. Study of antimicrobial, analgesic wound healing and antioxidant activities of some newly synthesized oxychinolin derivatives and their characterization. Beni-Suef Univ. J. Basic App. Sci., 2015, 4, 232-245.
Harmeet, K.; Balasubramanian, N. Antimicrobial activity of diazenyl derivatives: An update. Curr. Top. Med. Chem., 2018, 18, 3-21.
Ashishkumar, K.P.; Vishal Pankajkumar, M. Synthesis and biological activity of n-5-(4-methylphenyl) diazenyl-4-phenyl- 1, 3-thiazol-2-ylbenzamide derivatives. Quim. Nova, 2011, 34(5), 771-774.
Simona, C.; Lucia, S.; Anna, M.P.; Amalia, P.; Rosita, D. Pio Iannelli.; Stefano, P. Structure modification of an active azo-compound as a route to new antimicrobial compounds. Molecules, 2017, 22, E875.
Jyotirmaya, S.; Sudhir Kumar, P. A Study on antimicrobial evaluation of newly synthesized antipyrin analogues. Indian J. Pharm. Ed. Res., 2017, 4(51), 740-747.
Heena, S.; Mehul, Z.; Gourav, J.; Neha, K.; Amita, P. Design, synthesis, and biological evaluation of some new benzostyrene incorporated phenyl styryl ketone derivatives as COX-2 inhibitors with anti-inflammatory activity. Int. J. Pharm. Pharmaceutical Res., 2017, 2(10), 424-442.
Stefano, P.; Simona, C.; Lucia, S.; Rosita, D.; Gabriel, T.; Carlos, J. Ugo.; Cand Pio, I. Synthesis and antimicrobial studies of new antibacterial azo-compounds active against staphylococcus aureus and listeria monocytogenes. Molecules, 2017, 22, E1372.
Shweta, T.; Vikas, M. Vasudha Sharma.; Pushplata, S.; Manjul, S. Synthesis and evaluation of schiff’s base of 4-quinazolinone analogues as antimicrobial agents. Asian J. Pharmaceutical Clin. Res., 2012, 5(1), 98-100.
William, K.; Cedric, D.; Reimmel, K.A. Synthesis and evaluation of antimicrobial properties of azo dyes. Int. J. Pharm. Pharm. Sci., 2014, 7(4), 398-401.
Thangasamy, E.; Durairaj, P.B.; Gopalakrishnan, M. Synthesis, Spectral Analysis, in vitro microbiological evaluation, and molecular docking studies of some novel 1-(1-Aryl-1H-tetrazol-5-yl)-2-(piperidin-1-yl)ethanone derivatives. ISRN Org. Chem., 2014, 2014, 1-9.
Elias, K.M.; Jonathan, R.D.; Sarvesh, C.V.; Chandrasekar, P.H. Novel styryl ketones acted as novel fungicidal agent by inhibiting H+-ATPase-mediated proton pumping in Cryptococcus. J. Antimicrob. Chemother., 2001, 47, 491-494.
Vora, P.J.; Mehta, A.G. Synthesis, characterization and antimicrobial efficacy of quinoline based compounds. IOSR J. App. Chem., 2012, 4, 34-39.
Mohamad Syahir, M.S.; Oo Chuan, W.; Yam Mun, F. Synthesis, characterisation and vasolidation properties of indanone-based chalcones. J. Phy. Sci., 2018, 29(Suppl. 1), 99-106.
Moses, N.N.; Grace, N.A.; Hermia, N.I.; Denis, Z.; Fidele, N.K.; Simon, M.N.E. Structurally simple synthetic 1, 4-disubstituted piperidines with high selectivity for resistant Plasmodium falciparum. BMC Pharmacol. Toxicol., 2018, 19, 1-7.
Simona, C.; Lucia, S.; Anna, M.P.; Amalia, P.; Rosita, D.; Pio, I.; Stefano, P. Structure modification of an active azo-compound as a route to new antimicrobial compounds. Molecules, 2017, 22, 875.
Sanchez, I.; Pujol Maria, D.; Guillaumet, G. Massingham Roy.; Andre M. Synthesis of new piperidine and cyclohexylamino-spiro derivatives as potential anticalcium agents. Sci. Pharm., 2002, 70, 177-187.
Anand, K.H.; Bhashkar, B.; Vasudha, S.; Raman, B.; Amit, K.; Ajay, S.; Kiran, T. Synthesis and in vitro antimicrobial studies of some new 3-[phenyldiazenyl] benzaldehyde N-phenyl thiosemicarbazones. J. Enzyme Inhib. Med. Chem., 2008, 23, 77-81.
Aastha, P.; Priyanka, R.; Navneet, K.; Pratima, S.; Kishore, D. An efficient synthesis and applications of chalcones in organic synthesis. Int. J. Chem. Pharm. Sci., 2013, 4, 19-23.
Siva, S.R.L.; Bhagavanraju, M.; Sridhar, C. Synthesis and evaluation of novel morpholine linked substituted chalcone derivatives. Med. Chem., 2015, 2015, 133-141.
Siva, S.R.L.; Bhagavanraju, M.; Sridhar, C. Synthesis and evaluation of novel pyrrolidine chalcone derivatives with anticancer, anti-inflammatory and antibacterial activities. J. Chem. Pharm. Res., 2015, 7, 211-219.
Boon, K.H.; Zainab, N.; Paul, M.N.; Siaw, S.H.; Reagan, E.L.; Ee, L.K.; Boon, K.L. Synthesis and anticancer activities of 4-[(halophenyl)diazenyl]phenol and 4-[(halophenyl)diazenyl]phenyl aspirinate derivatives against nasopharyngeal cancer cell lines. J. Chem., 2017, 2017, 1-7.
Mohammed, R.A.; Girija, S.V.; Nasreen, B.; Syed, A. Synthesis of novel chalcone derivatives by conventional and microwave irradiation methods and their pharmacological activities. Arab. J. Chem., 2016, 9, 931-935.
Shailendra, M.; Hemendra, P.; Dutta, G.S.; Hari Narayana Moorthy, N.S. Synthesis and characterization of some chalcone derivatives. Trends Appl. Sci. Res., 2007, 2, 52-56.
Prasada, R.M.M.; Dhachinamoorthi, D.; Mounika, M. Pavan,i M. Shireennaaz, S.; Sravani Reddy, C.; Sri Annapurna, M. Synthesis, characterization and anti microbial activity of novel chalcones and its di hydro pyrimidinenones. Int. J. Life Sci. Pharma Res., 2015, 5, 13-16.
Rajendra, P.Y.; Praveen Kumar, P.; Ravi Kumar, P.; Srinivasa Rao, A. Synthesis and antimicrobial activity of some new chalcones of 2-Acetyl Pyridine. E-J. Chem., 2008, 5, 144-148.
Maria, C.S.L.; Marcus de Souza, V.N.; Alessandra, P.C.; Marcelle de Ferreira, L.; Raoni, G.S.B.; Thais, C.N.M.; Monica, P.A. Evaluation of anti tubercular activity of nicotinic and isoniazid analogues. ARKIVOC, 2007, 15, 181-191.
Lisa, A.C.; Scott, G.F. Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium. Antimicrob. Agents Chemother., 1997, 41, 1004-1009.
Vanithaa, J.D.; Paramasivan, C.N. Evaluation of microplate Alamar blue assay for drug susceptibility testing of Mycobacterium avium complex isolates. Diagn. Microbiol. Infect. Dis., 2004, 49, 179-182.
Kimberly, K.; Repp, S.A.; Menor Robin, K.P. Microplate Alamar blue assay for susceptibility testing of Candida albicans biofilms. Med. Mycol., 2007, 45, 603-607.
Schwalbe, R.; Lyn Steele, M.; Avery Goodwin, C. Antimicrobial susceptibility testing protocols. Crc Press. May 22, 2007.
Shrinath, S.M.; Basavaraj, R.P.; Aishakhanam, H.P.; Ganesh, N.K.; Shashikala, G.L.; Kalagouda, B.G. Synthesis, antimicrobial and antimycobacterial evaluation of star shaped hydrazones derived from 1,3,5-triazine. Der. Pharma Chemica., 2012, 4(2), 600-607.
Daniel Chu, T.W.; Prabhavathi Fernandesh, B. Mini review- structural activity relationships of fluoroquinolones. Antimicrob. Agents Chemother., 1989, 33(2), 131-135.
Prabodh, C.S.; Ankit, J.; Sandeed, J. Fluoroquinolone antibacterials- A review on chemistry, microbiology and therapeutic prospects. Acta Pol. Pharm., 2009, 66(6), 587-604.

open access plus

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 19 December, 2018
Page: [28 - 38]
Pages: 11
DOI: 10.2174/2211352516666180927111546

Article Metrics

PDF: 54