SYNTHESIS OF SOME NEW ANTIMICROBIAL 5,6,7,8-TETRAHYDROPYRIMIDO [4,5-b] QUINOLONE DERIVATIVES
HTML Full TextPOTENT ANTIMICROBIAL TETRAHYDROPYRIMIDOQUINOLINE DERIVATIVES
Sherif M. Sherif * 1 and Huda R. M. Rashdan 2
Department of Chemistry 1, Faculty of Science, Cairo University, (Dean of Faculty of Science, Cairo University), Giza 12613, Egypt.
Department of Chemistry of Natural and Microbial Products 2, Pharmaceutical and Drug Industries Research Division, National Research Center, Giza, Egypt.
ABSTRACT: 2-Amino-1-aryl-1, 4, 5, 6, 7, 8-hexahydro-4-phenyl-quinoline-3-carbonitrile derivatives were synthesized by the reaction of cyclohexanone (1) with 2-benzylidine-malononitrile (2) and the appropriate of aniline derivatives. The reactivity of some of these newly synthesized derivatives toward carbon disulfide and further toward hydrazonoyl halides were also studied. Also, the antimicrobial activity of the newly synthesized derivatives was reported.
Keywords: |
Tetrahydroquinoline, Pyrimidoquinolines, Hydrazonoyl halides, Antimicrobial activity
INTRODUCTION: The biological and pharmaceutical importance of pyrimidoquinoline derivatives stimulated the recent interest in the synthesis of these ring systems. This biological importance includes antimalarial 1, anticancer 2, antimicrobial 3, 4 and anti-inflammatory activities 5, 6. Recently, there has also been considerable interest in the synthesis of tetra hydroquinolines and their fused derivatives 7-11. The aim of the work presented herein was to synthesize pyrimido [4,5-b] quinolones using tetrahydro quinoline carbonitriles as building blocks. Such a synthesis of condensed azines is of biological interest due to the isoelectronic relationship that exists between the pyrimidine ring and tetrahydroquinoline 12-23.
RESULT AND DISCUSSION: The reaction of cyclohexanone (1) with 2-benzylidine-malono-nitrile (2) and the appropriate of 4-flouroaniline in ethanol (20) ml afforded 2-amino-1-(4-fluorophenyl)-1,4,5,6,7,8-hexahydro - 4 – phenyl-quinoline – 3 -carbonitrile (3) Scheme 1.
Compound 3 reacted with carbon disulfide to yield the target ring system 8 through the intermediates 6 and 7, whose subsequent rearrangement leads to the fused pyrimidinedione 8 Scheme 2.
Compound 8 reacted with the appropriate of hydrazonoyl halides in chloroform in the presence of catalytic amount of triethylamine under reflux to give the corresponding derivatives 9a-c, 10 and 11a, b the structure of these compounds confirmed by elemental analysis, spectral data (IR, NMR, Mass) where, compound 9a showed IR signals at 1735(C=O), 2937, 2868(CH-aliphatic) and showed H1NMR signals at 1.22-2.89(m, 11H, 4CH2, 3H-CH2CH3), 4.3-4.35(q, 2H, CH2CH3), 4.7(s, 1H, CH), 7.30-7.54(m, 13H, Ar-H).
Also, compound 10 showed IR signals at 1680(C=O), 2936, 2871(CH-aliphatic) and H1NMR signals at 1.40-2.81(m, 8H, 4CH2), 4.67(s, 1H, CH), 7.13-7.59(m, 18H, Ar-H) Scheme 3.
SCHEME 1
SCHEME 2
SCHEME 3
Biological Activity: Screening of antimicrobial activity was performed at a Microbiology Lab in the Faculty of Agriculture, El-Azhar University, Cairo, Egypt. All the tested microorganisms were chosen on the bases of their pathogenicity. Where, Aspergillus caused a broad spectrum of disease in the human host, ranging from hypersensitivity reactions to direct angioinvasion. Aspergillus primarily affects the lungs, causing four main syndromes, including allergic bronchopulmonary aspergillosis (ABPA), chronic necrotizing Aspergillus pneumonia (or chronic necrotizing pulmonary aspergillosis [CNPA]), aspergilloma, and invasive aspergillosis. However, in patients who are severely immunocompromised, Aspergillus may hematogenously disseminate beyond the lung, potentially causing endophthalmitis, endocarditis, and abscesses in the myocardium, kidney, liver, spleen, soft tissue, and bone. On the other hand, Candida albicans is a diploid fungus that grows both as yeast and filamentous cells and a causal agent of opportunistic oral and genital infections in humans 24, 25.
C. albicans have emerged as important causes of morbidity and mortality in immunocompromised patients (e.g., AIDS, cancer chemotherapy, organ or bone marrow transplantation). Also, Staphylococcus aureus can cause a range of Illnesses, from minor skin infections, such as pimples, impetigo, boils (furuncles), cellulitis folliculitis, carbuncles, scalded skin syndrome, and abscesses, to life-threatening diseases such as pneumonia, meningitis, osteomyelitis, endocarditis, toxic shock syndrome (TSS), bacteremia, and sepsis. Its incidence ranges from the skin, soft tissue, respiratory, bone, joint, endovascular to wound infections.
It is still one of the five most common causes of nosocomial infections and is often the cause of postsurgical wound infections. Each year, some 500,000 patients in American hospitals contract a staphylococcal infection 26. Also, some Bacillus species can cause food poisoning; Bacillus can result in two different kinds of intoxications.
It can either cause nausea, vomiting, and abdominal cramps for 1-6 h, or diarrhea and abdominal cramps for 8-16 h. The food poisoning usually occurs from eating rice that is contaminated with Bacillus subtilis (EMBL EBI), Some Bacillus organisms can cause more severe illnesses, for example, causes Anthrax. Also, Salmonella typhimurium is a pathogenic Gram-negative bacteria predominately found in the intestinal lumen. Its toxicity is due to an outer membrane consisting largely of lipopolysaccharides (LPS) which protect the bacteria from the environment.
Salmonella typhimurium causes gastroenteritis in humans and other mammals. And finally, pathogenic strains of E. coli are responsible for three types of infections in humans: urinary tract infections (UTI), neonatal meningitis, and intestinal diseases (gastroenteritis).
Representative derivatives 3, 4, 5, 8, 9a, 9b, 9c, 10, 11a and 11b were selected and tested for their antimicrobial activity against two gram(+) bacteria (Staphylococcus aureus, Bacillus subtilis), two gram(-) bacteria (Escherichia coli, salmonella Typhimurium) and a filamentous fungus (Aspergillus fumigatus) and a diploid fungus (Candida albicans). Using the modified Kirby-Bauer disc diffusion method 27, 28, 29. For the disc diffusion, the zone diameters were measured with slipping calipers of the national committee for clinical laboratory standards 30. The results are given in Table 1.
TABLE 1: RESPONSE OF VARIOUS MICROORGANISMS TO SOME SYNTHESIZED COMPOUNDS IN IN-VITRO CULTURE
Inhibition zone diameter (mm/mg sample)
Antimicrobial activity% |
||||||
Sample | A. fumigatus | C. albicans | S. aureus | B. subtilis | E. coli | S. typhimurium |
DMSO (positive control) | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
Tetracycline
(Antibacterial agent) |
-- | -- | 30 | 29 | 31 | 30 |
Clotrimazole
(Antifungal agent) |
24 |
22 |
-- |
-- |
-- |
-- |
3 | 22
92% |
16
73% |
23
77% |
22
76% |
24
77% |
27
90% |
4 | 14
58% |
8
36% |
17
57% |
16
55% |
17
55% |
14
47% |
5 | 16
67% |
7
32% |
15
50% |
10
34% |
12
50% |
15
50% |
8 | 9
38% |
0.00
0.00 |
21
70% |
12
41% |
5
16% |
0.00
0.00 |
9a | 12
50% |
9
41% |
5
17% |
12
41% |
19
61% |
14
47 |
9b | 19
79% |
18
82% |
9
30% |
23
79% |
25
81% |
23
77% |
9c | 15
63% |
5
23% |
3
10% |
14
48% |
11
35% |
10
33% |
10 | 10
42% |
12
55% |
14
47% |
0.00
0.00 |
0.00
0.00 |
0.00
0.00 |
11a | 4
17% |
0.00
0.00 |
12
40% |
14
48% |
14
45% |
12
40% |
11b | 14
58% |
0.00
0.00 |
23
77% |
22
76% |
23
74% |
25
83% |
Antimicrobial activity % = Inhibition zone diameter of the tested sample × 100 / Inhibition zone diameter of the standard
Strong effect means: antimicrobial activity% ≥ 60%
Moderate effect means: 60%>antimicrobial activity%≥40%
Weak effect means: 40%>antimicrobial activity%≥ 1%
No effect means: antimicrobial activity%=0.00%
CONCLUSION: The varied biological activities of the newly synthesized compounds promoted us to synthesize some new derivatives of these ring systems and study their antimicrobial activities, their biological activities depended mainly on the nature and the position of the substituents. The antifungal activity studies revealed that compounds 3, 5, 9b and 9c show strong effects against Aspergillus fumigatus. Also, compounds 3 and 9b show strong effects against Candida albicans. On the other hand compounds 3, 8 and 11b display strong effects against Staphylococcus aureus. Compounds 3, 9b and 11b give strong effects against Bacillus subtilis. Compounds 3, 9a, 9b and 11b show strong effects against Escherichia coli. And finally compounds 3, 9b and 11b afford strong effects against Salmonella Typhimurium. All the other compounds show effects against different types of tested microorganisms ranged from negative effects to moderate effects.
So we can say that the synthesis of new derivatives of these compounds is still an active area of research. Where synthesis and study of the antimicrobial activities of new analogous of these compounds will be helpful for a medicinal chemist to focus design of novel chemical entities containing pyrimidoquinoline derivatives as a part of antimicrobial drugs.
Experimental:
Experimental Instrumentation: All melting points were determined on an electrothermal apparatus and are uncorrected. IR spectra were recorded (KBr discs) on Shimadzu FT-IR 8201 PC spectrophotometer. H1NMR and spectra were recorded in CDCl3 and (CD3)2SO solutions on a Varian Gemini 300 MHz FT-NMR system spectrometer and chemical shifts are expected in δ ppm units using TMS as an initial reference. Mass spectra were recorded on GC-MS QP1000 EX Shimadzu. Elemental analyses were carried out at the Microanalytical Center of Cairo University. Hydrazonoyl halides 31, 32 were prepared as previously reported.
Synthesis:
2-amino–1 - (4 - flourophenyl) - 1, 4, 5, 6, 7, 8-hexahydro-4-phenylquinoline-3-carbonitrile (3): A mixture of cyclohexanone (1) (1 ml, 10 mmol), 2-benzylidinemalononitrile (2) (1.5 gm, 10 mmol) and 2,6-dichloroaniline (1.6 gm, 10 mmol) in absolute ethanol (20 ml) was heated under reflux for 10-12 h. Then the reaction mixture left to cool to room temperature overnight. The solid obtained was recrystallized from ethanol to afford the corresponding compound 3 in a good yield. Yield: 84%; MP: 230-232 °C; FT-IR: 3419, 3340(NH2), 2933, 2864(CH-aliphatic), 2210(CN), 1647(C=C); H1NMR (300MHz, DMSO-d6): 1.64-2.77(m, 8H, 4CH2), 4.5(s,1H, CH), 5.7(s, 2H, NH2), 7.1-7.4(m, 8H, Ar-H); MS (El, m/z (%)): 397(M+2, 97%), 396(M+1, 15%), 395(M+, 100%); Anal. Calcd. For C22H19Cl2N3 (395): C, 66.67; H, 4.83; N, 10.60 Found: C, 66.68; H, 4.83; N, 10.61%.
2-amino - 1 - (4-bromophenyl) - 1, 4, 5, 6, 7, 8 -hexahydro-4-phenylquinoline-3-carbonitrile (4): A mixture of cyclohexanone (1) (1ml, 10 mmol), 2-benzylidinemalononitrile (2) (1,5gm, 10 mmol) and 4-bromoaniline (1.7 gm, 10 mmol) in absolute ethanol (20 ml) was heated under reflux for 10-12 hrs. Then the reaction mixture left to cool to room temperature overnight. The solid obtained was recrystallized from ethanol to afford the corresponding compound 3 in a good yield. Yield: 81%; MP: 275-277 °C; FT-IR: 3417, 3339(NH2), 2932, 2864(CH-aliphatic), 2209(CN), 1647(C=C); H1NMR: 1.45-2.8(m, 8H, 4CH2), 4.5(s, 1H, CH), 5.74(s, 2H, NH2), 7.3-7.5(m, 9H, Ar-H); (300MHz, DMSO-d6): MS (El, m/z(%)): (M+2, 92%), (M+1, 4%), (M+, 100%); Anal. Calcd. for C22H20BrN3 (405): C, 65.03 ; H, 4.96 4.29; N, 10.34 Found: C, 61.82; H, 4.28; N, 18.80%.
2-amino- 1 - (3-bromophenyl) - 1, 4, 5, 6, 7, 8 -hexahydro-4-phenylquinoline-3-carbonitrile (5): A mixture of cyclohexanone (1) (1 ml, 10 mmol), 2-benzylidinemalononitrile (2) (1.5 gm, 10 mmol) and 3-bromoaniline (1.7 gm, 10 mmol) in absolute ethanol (20 ml) was heated under reflux for 10-12 hrs. Then the reaction mixture left to cool to room temperature overnight. The solid obtained was recrystallized from ethanol to afford the corresponding compound 3 in a good yield. Yield: 78%; MP: 286-288 °C; FT-IR: 3418, 3339(NH2), 2931, 2864(CH-aliphatic), 2212(CN), 1647(C=N); H1NMR: 1.45-2.8(m, 8H, 4CH2), 4.5(s, 1H, CH), 5.72(s, 2H, NH2), 7.3-7.54(m, 9H, Ar-H); (300MHz, DMSO-d6): MS (El, m/z(%)): 407(M+2, 32%), 406(M+1, 45%), 405(M+, 34%); Anal. Calcd. C22H20BrN3 (405): C, 65.03; H, 4.96 4.29; N, 10.34 Found: C, 61.82; H, 4.28; N, 18.80%.
10 - (2,6-dichlorophenyl)-6, 7, 8, 9- tetrahydro-5-phenylpyrimido[4,5-b]quinoline-2,4(1H, 3H, 5H, 10H)-dithione (8): To a solution of 3(2 gm, 5 mmol) in dry pyridine (30 ml) carbon disulfide (5 mmol) was added and the reaction mixture was refluxed on water bath for 6 h then left to cool to room temperature, poured onto ice-cold water and neutralized with diluted hydrochloric acid to complete precipitation. The solid obtained was filtered off, washed, dried well and recrystallized from methanol to give 8 as orange crystals. Yield: 78%; MP: 207-209 °C; FT-IR: 3300(NH), 2831, 2764(CH-aliphatic); H1NMR: 1.45-2.8(m, 8H, 4CH2), 4.5(s, 1H, CH), 7.32-7.54(m, 8H, Ar-H), 11.0(s, 2H, NH); (300MHz, DMSO-d6): MS (El, m/z(%)): 473(M+2, 98%), 472(M+1, 21%), 471(M+, 100%); Anal. Calcd. C23H19Cl2N3S (471): C, 58.47; H, 4.05; N, 8.89 Found: C, 58.46; H, 4.03; N, 8.88%.
General method for the synthesis of 9a-c, 10, 11a and 11b: A mixture of 8(4.7 gm, 10 mmol) and the appropriate of hydrazonoylhalides (10 mmol) was boiled under reflux in chloroform (30 ml) containing a catalytic amount of triethylamine (10 drops) for 12-15 h. The reaction mixture was left overnight for cooling, the solid collected and recrystallized from the proper solvent to give the corresponding 9a-c, 10, 11a and 11b respectively.
Ethyl (6, 10-diphenyl- 1 - (2, 6-dichlorophenyl)-7-thio-1, 2, 3, 4, 5, 6-hexahydro - 1, 7a, 9, 10, 11-pentaazacyclopenta[a]anthracene) acetate (9a): Yellow crystals from ethanol. Yield: 72%; MP: 194-196 °C ; FT-IR: 1735(C=O), 2937, 2868(CH-aliphatic); H1NMR: 1.22-2.89(m, 11H, 4CH2, 3H-CH2CH3), 4.3-4.35(q, 2H, CH2CH3), 4.7(s, 1H, CH), 7.30-7.54(m, 13H, Ar-H); (300MHz, DMSO-d6): MS (El, m/z(%)): 629(M+2, 73%), 628(M+1, 34%), 627(M+, 70%); Anal. Calcd. C33H27Cl2N5 O2S (627): C, 63.06; H, 4.33; N, 11.14 Found: C, 63.06; H, 4.33; N, 11.12%.
Ethyl (6-phenyl – 10 - (p-chlorophenyl)-1-(2, 6 -dichlorophenyl)-7- thio- 1,2,3,4,5,6-hexahydro-1, 7a, 9,10,11-pentaazacyclopenta [a] anthracene) acetate(9b): Yellow crystals from ethanol. Yield: 74%; MP: 187-189 °C; FT-IR: 1739(C=O), 2939, 2878(CH-aliphatic); H1NMR: 1.20-2.87(m, 11H, 4CH2, 3H-CH2CH3), 4.31-4.35(q, 2H, CH2CH3), 4.7(s, 1H, CH), 7.33-7.52(m, 12H, Ar-H); (300MHz, DMSO-d6): MS (El, m/z(%)): 665(M+2, 3%), 664(M+1, 70%), 663(M+, 4%); Anal. Calcd. C33H26Cl3N5O2S (663): C, 59.78; H, 3.95; N, 10.56 Found: C, 59.78; H, 3.95; N, 10.56%.
Ethyl (6-phenyl - 10 - (p-methylphenyl) – 1 - (2, 6 - dichlorophenyl)-7-thio-1,2,3,4,5,6-hexahydro-1,7a,9,10,11-pentaazacyclopenta [a] anthracene) acetate(9c): Yellow crystals from ethanol. Yield: 71%; MP: 190-192 °C; FT-IR: 1737(C=O), 2939, 2878(CH-aliphatic); H1NMR: 1.20-2.87(m, 14H, 4CH2, 3H-CH3, 3H-CH2CH3), 4.31-4.35(q, 2H, CH2CH3), 4.7(s, 1H, CH), 7.33-7.54(m, 12H, Ar-H); (300MHz, DMSO-d6): MS (El, m/z(%)): 643(M+2, 81%), 642(M+1, 27%), 641(M+, 80%); Anal. Calcd. C34H29Cl2N5O2S (641): C, 63.55; H, 4.55; N, 10.90 Found: C, 63.53; H, 4.55; N, 10.89%.
6,10-diphenyl -8-benzoyl-1-(2,6-dichlorophenyl)-7-thio-1, 2, 3, 4 ,5, 6- hexaahydro - 1, 7a, 9, 10, 11-pentaazacyclopenta[a]anthracene(10): Pale yellow crystals from ethanol. Yield: 79%; MP: 150-152 °C; FT-IR: 1680(C=O), 2936, 2871(CH-aliphatic); H1NMR: 1.40-2.81(m, 8H, 4CH2), 4.67(s, 1H, CH), 7.13-7.59(m, 18H, Ar-H); (300MHz, DMSO-d6): MS (El, m/z(%)): 661(M+2, 14%), 660(M+1, 27%), 659(M+, 13%); Anal. Calcd. C37H27Cl2N5OS (659): C, 67.27; H, 4.12; N, 10.60 Found: C, 67.27; H, 4.12; N, 10.61%.
6, 10-diphenyl-8-acetyl-1-(2, 6-dichlorophenyl)-7-thio-1,2,3,4,5,6-hexaahydro-1,7a,9,10,11-penta azacyclopenta [a] anthracene (11a): Yellow crystals from ethanol. Yield: 73%; MP: 163-165 °C; FT-IR: 1690(C=O), 2935, 2879(CH-aliphatic); H1NMR: 1.43-2.89(m, 11H, 4CH2, 3H-CH3), 4.7(s, 1H, CH), 7.33-7.54(m, 13H, Ar-H); (300MHz, DMSO-d6): MS (El, m/z(%)): 600(M+2, 9%), 599(M+1, 12%), 598(M+, 11%); Anal. Calcd. C32H25Cl2N5OS (598): C, 64.21; H, 4.21; N, 11.70 Found: C, 64.21; H, 4.22; N, 11.68%.
6-phenyl- 10 - (p-chlorophenyl) - 8 - acetl - 1 - (2, 6-dichlorophenyl)-7-thio-1, 2, 3,4,5,6-hexahydro-1, 7a, 9, 10, 11-pentaazacyclopenta[a]anthracene (11b): Yellow crystals from ethanol. Yield: 75%; MP: 171-173 °C; FT-IR: 1689(C=O), 2935, 2883(CH-aliphatic); H1NMR: 1.42-2.88(m, 11H, 4CH2, 3H-CH3), 4.7(s, 1H, CH), 7.33-7.54(m, 12H, Ar-H); (300MHz, DMSO-d6): MS (El, m/z(%)): 633(M+2, 75%), 632(M+1, 6%), 631(M+, 80%); Anal. Calcd. C32H24Cl3N5OS (631): C, 60.72; H, 3.82; N, 11.06 Found: C, 60.71; H, 3.81; N,11.04%.
ACKNOWLEDGEMENT: Nil
CONFLICT OF INTEREST: Nil
REFERENCES:
- Joshi AA and Viswanathan CL: Recent developments in antimalarials drug discovery. Anti-Infect Agent Med Chem 2006; 5: 105-122.
- Dlugosz A and Dus D: Synthesis and anticancer properties of pyrimido[4,5-b]quinolines. Farmaco 1996; 51: 364-374.
- El-Sayed OA, El-Bieh FM and Al-Bassam BA: Novel 4-aminopyrimido[4,5-b]quinolone derivatives as potential antimicrobial agents. Boll Chim Farm 2002; 141: 461-465.
- El-Sayed OA, Al-Bassam BA and Hussein ME: Synthesis of some novel quinoline-3-carboxylic acids and pyrimidoquinoline derivatives as potential antimicrobial agents. Arch Pharm (Weinheim) 2002; 335: 403-410.
- Gavrilov MY, Mardanova LG, Kolla VE and Konshin ME: Synthesis, anti-inflammatory and analgesic activities of tetrahydroquinioline-3-carboxamides. Pharm Chem J 1988; 22: 554-556.
- El-Sayed OA, Al-Turki TM, Al-Daffiri HM, Al-Bassam BA and Hussein ME: Pyrimidoquinoline derivatives as anti-inflammatory and antimicrobial agents. Boll Chim Farm 2004, 143, 227-238.
- Al-Mousawi SM, Elkholy YM, Mohammed MA and Elnagdi MH: Synthesis of new condensed 2-amino-4H-pyran-3-carbonitriles and of 2-Aminoquinoline-3-carbonitriles. Org Prep Proceed Int 1999; 31: 205-214.
- Elassar AA and Elkholy YM: Synthesis of 3,4,7-triazaacenaphthylene and pyrido[3,4,5-de]cinnoline derivatives. Heteroatom Chem 2003; 14: 427-433.
- Elkholy YM: Studies with polyfunctional substituted heterocycles. Chem Heterocycl Comp 2002; 38: 1342-1347.
- Elkholy YM: Synthesis and antimicrobial of new polyfunctional substituted pyridazines and their derivatives. Heterocycl Commun 2005; 11: 89-96.
- Asolkar RN, Schroder D, Heckmann R, Land S, Wagner-Dobler I and Laatsch H: Helquinoline, a new tetrahydroquinoline antibiotic from Janibacter limosus Hel. J Antibiotics 2004; 57: 17-23.
- Schoenwald RD: Tetrahydroquinoline analogs for use in glaucoma treatment; U.S. Pat.5776482, 1988.
- Dimon DB and Robert W: Preparation of 4-carboxy amino-2-substituted tetrahydroquinoline derivatives as cholesteryl ester transfer protein inhibitors; JP 2001; 163859.
- Shaaban MA, Ghoneim KM and Kalifa M: Synthesis of certain 4-oxo-tetrahydroquinoline and benzauocine derivatives likely to possess analgesic activity. Pharmazie 1977; 32: 90-92.
- Hashimoto K, Okaichi Y, Nomi D, Bando M and Minamikawa J: A practical synthesis of (S)-(−)-nadifloxacin: Novel acid-catalyzed racemization of tetrahydroquinoline derivatives. Chem Pharm Bull 1996; 44: 642-645.
- Chakaravorty PK and Grelnlee WPCT: Int. Appl WO 92, 20,687,156, 1992; [C.A. 1993, 118, 213104d].
- Shujiang TU, Fang F, Tuanjie L, Songlei Z and Xiaojing Z: An efficient one-pot synthesis of the novel pyrimidoquinoline derivative under microwave irradiation without a catalyst. J Heterocycl Chem, 2005; 42: 707-710.
- Shimamure H, Terajima K and Kawase Y: Jpn Kokai Tokyo Koho JP 05,112,559, 1993.
- Gavrilov M and Konshin ME: Synthesis of Octahydro-quinoline[4,5-b]quinoline-2,4-dione. Chem Heterocycl Comp 1989; 25: 932-935.
- Abdel-Gawad SM, El-Gagy MSA, Heiba HI, Aly HM and Ghorab MM: Synthesis and radiation stability of some new biologically active hydroquinoline and pyrimido[4,5-b] quinolone derivatives. J Chi Che Soc 2005; 52: 1227-1236.
- Abu-Shanab FA, Elkholy YM and Elnagdi MH: Enaminones as building blocks in organic Synthesis. Synth Commun 2002; 32: 3493-3502.
- Leoncini G, Signorello MG, Grossi GC and Di Braccio M: Mechanism of action of two new pyrimidoquinoline and isoquinoline derivatives in human platelets. Thromb Res 1997; 87: 483-492.
- Omura S and Nakagawa A: Structure of virantmycin, a novel antiviral antibiotic. Tetrahedron Lett 1981: 2199-2202.
- Ryan KJ and Ray CG: Sherris Medical Microbiology (4th). McGraw Hill 2004: ISBN 0-8385-8529-9.
- Enfert C and Hube B: Candida: Comparative and Functional Genomics. Caister Academic Press 2007; ISBN 9781904455134
- Bowersox, John (27 May 1999). "Experimental Staph Vaccine Broadly Protective in Animal Studies". NIH. Archived from the original on 5 May 2007.
- Bauer AW, Kibry AW, Sherris C and Turck M: American J of clinical pathology 1966; 45: 493-496.
- Pfaller MA, Burmeister L, Bartlett MA and Rinaldi MG: J Clinical Microbiol 1988; 26: 1437-1441,
- National Committee for Clinical Laboratory Standards, 1993, performance vol. 41, antimicrobial susceptibility of Flavobacteria 1997.
- National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved Standard M7-A3. National Committee for Clinical Laboratory Standards, Villanova, Pa 1993.
- Shawali AS and Abdelhamid AO: Bull Soc Chem Jpn 1976; 49: 321-332.
- Eweiss NF and Osman A: J Hetterocycl Chem 1980; 17: 1713-1717.
How to cite this article:
Sherif SM and Rashdan HRM: Potent antimicrobial tetrahydropyrimidoquinoline derivatives. Int J Pharmacognosy 2015; 2(1): 21-27. doi: 10.13040/IJPSR.0975-8232.2(1).21-27.
This Journal licensed under a Creative Commons Attribution-Non-commercial-Share Alike 3.0 Unported License.
Article Information
4
21-27
671
1296
English
Ijp
S. M. Sherif * and H. R. M. Rashdan
Department of Chemistry, Faculty of Science, Ain-Shams University, Cairo, Egypt.
hudadawoud20@yahoo.com
20 June 2014
27 December 2014
30 December 2014
http://dx.doi.org/10.13040/IJPSR.0975-8232.IJP.2(1).21-27
01 January 2015