Generic placeholder image

Current Organic Synthesis


ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

Research Article

Synthesis and Antimicrobial Evaluation of Some Novel Pyrimidine, Pyrazole, Chromene and Tetrahydrobenzo[b]thiophene Derivatives Bearing Pyrimidinthione Moiety

Author(s): Mohamed Ahmed Mahmoud Abdel Reheim*, Ibrahim Saad Abdel Hafiz and Mohamed Ahmed Elian

Volume 17 , Issue 7 , 2020

Page: [548 - 557] Pages: 10

DOI: 10.2174/1570179417666200628021125

Price: $65


Aim and Objective: A novel collection of fused pyrimidine, pyridine, pyrazole, chromene and thiophene derivatives 2-30 have been newly synthesized by using the 1a, b as starting material. Fused pyrane exhibits a range of pharmacological activity such as cancer agents [1], antimicrobial [2-4], antioxidant [5], antiproliferative [6], cytotoxic activity [7], anticipated antitumor [8], antiparkinsonian [9] and anti-inflammatory [10]. Moreover, pyrane derivatives are well known for bacterial biofilm disruptor [11], anticonvulsant [12] and inhibitors of mycobacterium bovis [13].

Materials and Methods: All melting points were measured using the Akofler Block instrument and are uncorrected. IR spectra (KBr) were recorded on a FTIR 5300 spectrometer (υ, cm-1). The 1H-NMR spectra were recorded on a Varian Gemini spectrometer. The 1H-NMR spectra were run at 300, 400 MHz and 13C-NMR spectra were run at 100 MHz in DMSO-d6, CDCl3 as solvents. The chemical shifts are expressed in parts per million (ppm) by using tetramethylsilane (TMS) as an internal reference, 1000 EX mass spectrometer at 70 eV. The purity of synthesized compounds was checked by thin-layer chromatography (TLC) (aluminum sheets) using nhexane, EtOAc (9:1, V/V, 7:3 V/V) eluent. Elemental analyses were carried out by the Microanalytical Research Center, Faculty of Science, and Microanalytical Unit, Faculty of Pharmacy, Cairo University, Egypt.

Results and Discussion: A novel series of azoles and azines were designed and prepared via the reaction of 7-amino- 5-(4-chlorophenyl)-4-phenyl-2-thioxo-2,5-dihydro-1H-pyrano- [2,3-d]pyrimidine-6-carbonitrile 1a and 7-amino-4,5- diphenyl-2-thioxo-2,5-dihydro-1H-pyrano[2,3-d]-pyrimidine-6-carbonitrile 1b with some electrophilic and nucleophilic reagents. The structures of target compounds were confirmed by elemental analyses and spectral data. The novel synthesized compounds showed good antimicrobial activity against the previously mentioned microorganisms.

Conclusion: In conclusion, compounds 1a, 1b underwent ready cyclization to give fused heterocyclic compounds through reaction with different reagents and under different conditions and subjected to antimicrobial screening.

Keywords: Antimicrobial activity, chromene, pyranopyridine, pyranopyrimidine, thiophene, thiopyrimidine.

Graphical Abstract
Räder, A.F.B.; Reichart, F.; Weinmüller, M.; Kessler, H. Improving oral bioavailability of cyclic peptides by N-methylation. Bioorg. Med. Chem., 2018, 26(10), 2766-2773.
[] [PMID: 28886995]
Tyumkina, T.V.; Makhmudiyarova, N.N.; Kiyamutdinova, G.M.; Meshcheryakova, E.S.; Bikmukhametov, K.S.; Abdullin, M.F.; Khalilov, L.M.; Ibragimov, A.G.; Dzhemilev, U.M. Synthesis, molecular structure, conformation and biological activity of Ad-substituted N-aryl-tetraoxaspiroalkanes. Tetrahedron, 2018, 74(15), 1749-1758.
Gaffer, H.; Khattab, T. Synthesis and characterization of some azo-heterocycles incorporating pyrazolopyridine moiety as disperse dyes. Egypt. J. Chem., 2017, 60, 41-47.
Hameed, A.; Al-Rashida, M.; Uroos, M.; Ali, S.A. Arshia; Ishtiaq, M.; Khan, K.M. Quinazoline and quinazolinone as important medicinal scaffolds: a comparative patent review (2011-2016). Expert Opin. Ther. Pat., 2018, 28(4), 281-297.
[] [PMID: 29368977]
Khattab, T.A. Synthesis and Self‐assembly of Novel s‐Tetrazine‐based Gelator. Helv. Chim. Acta, 2018, 101(4)e1800009
Yu, J.; Maliutina, K.; Tahmasebi, A. A review on the production of nitrogen-containing compounds from microalgal biomass via pyrolysis. Bioresour. Technol., 2018, 270, 689-701.
[] [PMID: 30206030]
Khattab, T.; Haggag, K.M. Synthesis and spectral properties of symmetrical and asymmetrical 3-cyano-1, 5-diarylformazan dyestuffs for dyeing polyester fabrics. Egypt. J. Chem., 2017, 60, 33-40.
El-Messery, T.M.; Mwafy, E.A.; Mostafa, A.M.; Fakhr El-Din, H.M.; Mwafy, A.; Amarowicz, R.; Ozçelik, B. Spectroscopic studies of the interaction between isolated polyphenols from coffee and the milk proteins. Surf. Interfaces, 2020, 20100558
Kalaria, P.N.; Karad, S.C.; Raval, D.K. A review on diverse heterocyclic compounds as the privileged scaffolds in antimalarial drug discovery. Eur. J. Med. Chem., 2018, 158, 917-936.
[] [PMID: 30261467]
Khattab, T.A.; Abdelrahman, M.S.; Rehan, M. Textile dyeing industry: environmental impacts and remediation. Environ. Sci. Pollut. Res. Int., 2020, 27(4), 3803-3818.
[] [PMID: 31838699]
Khattab, T.A.; Fouda, M.M.G.; Abdelrahman, M.S.; Othman, S.I.; Bin-Jumah, M.; Alqaraawi, M.A.; Al Fassam, H.; Allam, A.A. Co-encapsulation of enzyme and tricyanofuran hydrazone into alginate microcapsules incorporated onto cotton fabric as a biosensor for colorimetric recognition of urea. React. Funct. Polym., 2019, 142, 199-206.
Darwish, W.M.; Darwish, A.M.; Al-Ashkar, E.A. Synthesis and nonlinear optical properties of a novel indium phthalocyanine highly branched polymer. Polym. Adv. Technol., 2015, 26(8), 1014-1019.
Nour, H.F.; El Malah, T.; Khattab, T.A.; Olson, M.A. Template-assisted hydrogelation of a dynamic covalent polyviologen-based supramolecular architecture via donor-acceptor interactions. Mater. Today Chem., 2020, 17100289
El-Saied, H.; Mostafa, A.M.; Hasanin, M.S.; Mwafy, E.A.; Mohammed, A.A. Synthesis of antimicrobial cellulosic derivative and its catalytic activity. J. King Saud Univ. Sci., 2020, 32(1), 436-442.
Khattab, T.A.; Rehan, M. Synthesis and characterization of bis-azo 1, 2, 4, 5-tetrazine dyestuff. J. Text. Color. Polym. Sci., 2018, 15(1), 33-36.
Kumari, S.; Kishore, D.; Paliwal, S.; Chauhan, R.; Dwivedi, J.; Mishra, A. Transition metal-free one-pot synthesis of nitrogen-containing heterocycles. Mol. Divers., 2016, 20(1), 185-232.
[] [PMID: 26055184]
Khattab, T.A.; Rehan, M. A Review on synthesis of nitrogen-containing heterocyclic dyes for textile fibers-part 2: Fused heterocycles. Egypt. J. Chem., 2018, 61(6), 989-1018.
Gerlach, K.; Hobson, S.; Eickmeier, C.; Groß, U.; Braun, C.; Sieger, P.; Garneau, M.; Hoerer, S.; Heine, N. Discovery of tetrahydroindazoles as a novel class of potent and in vivo efficacious gamma secretase modulators. Bioorg. Med. Chem., 2018, 26(12), 3227-3241.
[] [PMID: 29735425]
Indumathi, T.; Jamal Ahamed, V.S.; Moon, S.S.; Fronczek, F.R.; Rajendra Prasad, K.J. L-Proline anchored multicomponent synthesis of novel pyrido[2,3-a]carbazoles; investigation of in vitro antimicrobial, antioxidant, cytotoxicity and structure activity relationship studies. Eur. J. Med. Chem., 2011, 46(11), 5580-5590.
[] [PMID: 21983331]
Desai, N.C.; Pandya, D.D.; Bhatt, K.A.; Kotadiya, G.M.; Desai, P. Synthesis, antimicrobial, and cytotoxic activities of novel benzimidazole derivatives bearing cyanopyridine and 4-thiazolidinone motifs. Med. Chem. Res., 2014, 23(8), 3823-3835.
Mansoor, S.S.; Aswin, K.; Logaiya, K.; Sudhan, P.N.; Malik, S. Aqueous media preparation of 2-amino-4, 6-diphenylnicotinonitriles using cellulose sulfuric acid as an efficient catalyst. Res. Chem. Intermed., 2014, 40(2), 871-885.
Maqbool, M. Rational Design, Synthesis and Biological Screening of Cyanopyridine-Triazine Hybrids as Lead Multitarget Anti-Alzheimer Agents. Alzheimers Dement., 2017, 13(7), 627-633.
Grieco, M.; Polti, G.; Lambiase, L.; Cassini, D. Jejunal multiple perforations for combined abdominal typhoid fever and miliary peritoneal tuberculosis. Pan Afr. Med. J., 2019, 33, 51-56.
[] [PMID: 31448014]
Fletcher, S.; Keaney, E.P.; Cummings, C.G.; Blaskovich, M.A.; Hast, M.A.; Glenn, M.P.; Chang, S.Y.; Bucher, C.J.; Floyd, R.J.; Katt, W.P.; Gelb, M.H.; Van Voorhis, W.C.; Beese, L.S.; Sebti, S.M.; Hamilton, A.D. Structure-based design and synthesis of potent, ethylenediamine-based, mammalian farnesyltransferase inhibitors as anticancer agents. J. Med. Chem., 2010, 53(19), 6867-6888.
[] [PMID: 20822181]
Powers, J.H. Antimicrobial drug development--the past, the present, and the future. Clin. Microbiol. Infect., 2004, 10(Suppl. 4), 23-31.
[] [PMID: 15522037]
Brown, D. Antibiotic resistance breakers: Can repurposed drugs fill the antibiotic discovery void? Nat. Rev. Drug Discov., 2015, 14(12), 821-832.
[] [PMID: 26493767]
Clark, F. Discrimination against LGBT people triggers health concerns. Lancet, 2014, 383(9916), 500-502.
[] [PMID: 24516882]
Betrosian, A.P.; Frantzeskaki, F.; Xanthaki, A.; Georgiadis, G. High-dose ampicillin-sulbactam as an alternative treatment of late-onset VAP from multidrug-resistant Acinetobacter baumannii. Scand. J. Infect. Dis., 2007, 39(1), 38-43.
[] [PMID: 17366011]
Birben, E.; Sahiner, U.M.; Sackesen, C.; Erzurum, S.; Kalayci, O. Oxidative stress and antioxidant defense. World Allergy Organ. J., 2012, 5(1), 9-19.
[] [PMID: 23268465]
Reddy, D.S.; Hosamani, K.M.; Devarajegowda, H.C.; Kurjogi, M.M. A facile synthesis and evaluation of new biomolecule-based coumarin–thiazoline hybrids as potent anti-tubercular agents with cytotoxicity, DNA cleavage and X-ray studies. RSC Advances, 2015, 5(79), 64566-64581.
Mangasuli, S.N.; Hosamani, K.M.; Devarajegowda, H.C.; Kurjogi, M.M.; Joshi, S.D. Synthesis of coumarin-theophylline hybrids as a new class of anti-tubercular and anti-microbial agents. Eur. J. Med. Chem., 2018, 146, 747-756.
[] [PMID: 29407993]
Liu, X.; Deng, J.; Xu, Z.; Lv, Z.S. Recent advances of 2-Quinolone-based derivatives as anti-tubercular agents. Antiinfect. Agents, 2018, 16(1), 4-10.
Kalaria, P.N.; Satasia, S.P.; Avalani, J.R.; Raval, D.K. Ultrasound-assisted one-pot four-component synthesis of novel 2-amino-3-cyanopyridine derivatives bearing 5-imidazopyrazole scaffold and their biological broadcast. Eur. J. Med. Chem., 2014, 83, 655-664.
[] [PMID: 25010936]
Uttara, B.; Singh, A.V.; Zamboni, P.; Mahajan, R.T. Oxidative stress and neurodegenerative diseases: A review of upstream and downstream antioxidant therapeutic options. Curr. Neuropharmacol., 2009, 7(1), 65-74.
[] [PMID: 19721819]
Lalitha, M. Manual on antimicrobial susceptibility testing. Performance standards for antimicrobial testing. Twelfth Informational Supplement, 2004, 56238, 454-456.
da Silva, P.A.; Boffo, M.M.; de Mattos, I.G.; Silva, A.B.; Palomino, J.C.; Martin, A.; Takiff, H.E. Comparison of redox and D29 phage methods for detection of isoniazid and rifampicin resistance in mycobacterium tuberculosis. Clin. Microbiol. Infect., 2006, 12(3), 293-296.
[] [PMID: 16451420]
Abdel-Galil, E.; Abdel-Latif, E.; Haif, S.I.; Kandeel, E.E.M. Res. J. Pharm. Biol. Chem. Sci., 2016, 7(1), 1401-1407.
Winkel-Shirley, B. Biosynthesis of flavonoids and effects of stress. Curr. Opin. Plant Biol., 2002, 5(3), 218-223.
[] [PMID: 11960739]
Cushnie, T.P.; Lamb, A.J. Recent advances in understanding the antibacterial properties of flavonoids. Int. J. Antimicrob. Agents, 2011, 38(2), 99-107.
[] [PMID: 21514796]
Jackson, P.A.; Widen, J.C.; Harki, D.A.; Brummond, K.M. Covalent modifiers: A chemical perspective on the reactivity of α, β-unsaturated carbonyls with thiols via hetero-Michael addition reactions. J. Med. Chem., 2017, 60(3), 839-885.
[] [PMID: 27996267]
Dhamija, I.; Kumar, N.; Manjula, S.N.; Parihar, V.; Setty, M.M.; Pai, K.S.R. Preliminary evaluation of in vitro cytotoxicity and in vivo antitumor activity of Premna herbacea Roxb. in Ehrlich ascites carcinoma model and Dalton’s lymphoma ascites model. Exp. Toxicol. Pathol., 2013, 65(3), 235-242.
[] [PMID: 21920724]
Liao, S.; Shang, S.; Shen, M.; Rao, X.; Si, H.; Song, J.; Song, Z. One-pot synthesis and antimicrobial evaluation of novel 3-cyanopyridine derivatives of (-)-β-pinene. Bioorg. Med. Chem. Lett., 2016, 26(6), 1512-1515.
[] [PMID: 26898336]
Ayvaz, S.; Çankaya, M.; Atasever, A.; Altuntas, A. 2-Amino-3-cyanopyridine derivatives as carbonic anhydrase inhibitors. J. Enzyme Inhib. Med. Chem., 2013, 28(2), 305-310.
[] [PMID: 22141460]
Karki, R.; Thapa, P.; Kang, M.J.; Jeong, T.C.; Nam, J.M.; Kim, H.L.; Na, Y.; Cho, W.J.; Kwon, Y.; Lee, E.S. Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of hydroxylated 2,4-diphenyl-6-aryl pyridines. Bioorg. Med. Chem., 2010, 18(9), 3066-3077.
[] [PMID: 20392646]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy