Theoretical Study of Geometry of Quinazoline Derivatives and Their Antibacterial Activities
Ramandeep Kaur, Monika Bansal and Balbir Kaur*
Department of Chemistry, Punjabi University, Patiala 147002, Punjab, India
*Corresponding Author E-mail: aries_balbir@yahoo.co.in
ABSTRACT:
Quinazolines are a pharmacologically very attractive class of compounds. In the preliminary communication, 4-substituted phenyl-3,4,5,6-tetrahydrobenzo[h]quinazoline-2(1H)-thiones and their S-alkyl/aralkyl derivatives were synthesized. Through the Gaussian 03 studies, the expected stereochemistry of the synthesized compounds was checked. Also, the compounds were tested for antibacterial activities against Staphylococcus aureus, Pseudomonas fluorescence.
KEYWORDS: Quinazolines, Gaussian studies, Stereochemistry, Antibacterial activities
Fused pyrimidines1 are found in a broad variety of natural products, used in medicines, possess antimalarial activities4 and other important biological properties2,3,5,6. Recently, 1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione derivatives have been reported to exhibit potent calcium antagonist activities7 and have also attracted considerable attention owing to their potential antibacterial activity against Staphylococcus aureus and Pseudomonas fluorescence.
In line with the work on quinazoline derivatives, earlier, we have reported8 the synthesis of 4-substituted phenyl-3,4,5,6-tetrahydrobenzo[h]quinazoline-2(1H)-thiones through one-pot multicomponent reactions and then these quinazolinethiones were converted to S-alkyl/aryl quinazoline derivatives. The synthesized compounds were characterized on the basis of IR, NMR and mass spectral data. The present paper describes the study of expected geometries of these fused pyrimidine derivatives on the basis of Guassian 03 series of programs. Also, the quinazoline derivatives were tested for antibacterial effects. As a result, it was established that 2-ethylthio-4-(4-
hydroxy-3-methoxyphenyl)-1,4,5,6-tetrahydrobenzo [h]quinazoline was the most effective compound, which has caused growth inhibition of Staphylococcus aureus and Pseudomonas fluorescence (Table 7).
2. COMPUTATIONAL STUDIES:
The crystals suitable for X-ray analysis were not obtained. Therefore, the synthesized compounds were characterized through IR, NMR and Mass spectral values. The expected geometry, as per the literature, was obtained with computational studies by using Gaussian 03 series of programs. Bond lengths, Bond angles and dihedral angles were calculated from the geometries optimized with semiempirical methods. The X-ray study of the reference compound 1 taken, shows the boat shaped structure of pyrimidine ring and the substituted aryl ring is positioned axially, perpendicular to, and bisecting the boat like dihydropyrimidine ring, with the 4-aryl substituent (Z) adopting a synperiplanar orientation relative to C4-H (Figure 1).
Reference compound 1
Figure 1
It is clear from the AM1, MNDO, PM3 and PM3MM values of the prepared compounds that pyrimidine ring has taken somewhat elongated shape and 4-aryl ring is also not in the same plane as pyrimidine ring as is clear from the dihedral angle and bond angle values (Table 2, 3, 4, 5, 6) when compared with the reference compound 1 (Table 1). Therefore, it is expected that synthesized compounds (DHPMs) may exist in the expected boat confirmation as given in the literature9-13.
Already, studies have shown that as the solid state structure of dihydropyrimidine analogous can adopt a molecular conformation which is similar to the reported conformation of dihyhdropyridine calcium channel blockers. i. e. why dihydropyrimidines represent a heterocyclic system with remarkable pharmacological efficiency like that of dihydropyridine calcium channel blockers.
Table- 1-Selected Bond lengths (A0), Bond angles (0), dihedral angle(0)
|
Bond lenghts |
|
Bond angles |
|
Dihedral angles |
|
|
N1-C8 |
1.364 |
C9-C7-C6 |
112 |
C6-C7-C9-C14 |
-111 |
|
N1-C5 |
1.382 |
C9-C7-C2 |
111 |
C14-C9-C7-N2 |
+126 |
|
N2-C8 |
1.326 |
C7-C6-C5 |
120.1 |
C6-C7-C9-C10 |
+65 |
|
N2-C7 |
1.474 |
N2-C8-C1 |
116.3 |
C9-C7-N2-C8 |
92.1 |
|
C5-C6 |
1.358 |
N2-C7-C6 |
108 |
C9-C7-C6-C5 |
-98 |
|
C8-S1 |
1.678 |
N1-C5-C6 |
119.4 |
N2-C7-C6-C5 |
24.5 |
|
|
|
C7-N2-C8 |
124.8 |
|
|
|
|
|
C7-C6-C1 |
119.1 |
|
|
|
|
|
N1-C8-S1 |
120.6 |
|
|
|
|
|
N2-C8-S1 |
123.1 |
|
|
Compound 2
Table- 2
|
Parameters |
Compd.2 |
|
|
|
|
AM1 |
MNDO |
PM3 |
PM3MM |
|
|
Bond lenghts |
|
|
|
|
|
C4-N22 |
1.3889 |
1.3917 |
1.3969 |
1.3969 |
|
C1-N22 |
1.3959 |
1.4057 |
1.4151 |
1.4151 |
|
C4-N21 |
1.39 |
1.3934 |
1.3985 |
1.3985 |
|
C3-N21 |
1.398 |
1.4091 |
1.42 |
1.4204 |
|
C3-C2 |
1.4359 |
1.4509 |
1.419 |
1.414 |
|
C4-S23 |
1.614 |
1.5844 |
1.6548 |
1.6548 |
|
Bond angles |
|
|
|
|
|
C24-C1-C2 |
123.4746 |
126.345 |
124.533 |
124.533 |
|
N22-C1-C24 |
117.7336 |
115.7887 |
116.5597 |
116.5597 |
|
C1-C2-C3 |
119.0535 |
119.7613 |
118.9744 |
118.9744 |
|
N21-C4-C22 |
117.7718 |
114.8402 |
115.7969 |
115.7969 |
|
N22-C1-C2 |
118.7918 |
117.8663 |
118.9073 |
118.9073 |
|
C2-C3-N21 |
118.3407 |
116.4323 |
118.9632 |
118.9632 |
|
C1-N22-C4 |
122.8139 |
125.139 |
123.5417 |
123.5417 |
|
C1-C2-C5 |
122.0186 |
122.6018 |
122.3466 |
122.3466 |
|
N21-C4-S23 |
120.9942 |
122.4943 |
122.0079 |
122.0079 |
|
N22-C4-S23 |
121.2338 |
122.6655 |
122.144 |
122.144 |
|
Dihedral angles |
|
|
|
|
|
C2-C1-C24-C25 |
-47.7894 |
-90.1107 |
-55.1944 |
-55.1944 |
|
N22-C1-C24-C25 |
132.2036 |
89.881 |
124.7289 |
124.7289 |
|
C2-C1-C24-C26 |
133.7975 |
90.0937 |
125.6941 |
125.6941 |
|
C24-C1-N22-C4 |
-175.7451 |
179.971 |
179 |
179.2425 |
|
C24-C1-C2-C3 |
175.0909 |
-179.9975 |
177.2947 |
177.2947 |
|
N22-C1-C2-C3 |
-4.9019 |
0.011 |
-2.627 |
-2.627 |
Compound 3
Table- 3
|
Parameters |
Compd.3 |
|
|
|
|
AM1 |
MNDO |
PM3 |
PM3MM |
|
|
Bond lenghts |
|
|
|
|
|
C12-N34 |
1.3339 |
1.3283 |
1.3369 |
1.3369 |
|
C11-N34 |
1.3838 |
1.376 |
1.3795 |
1.3795 |
|
C12-N35 |
1.4159 |
1.4119 |
1.4272 |
1.4272 |
|
C8-N35 |
1.4063 |
1.4195 |
1.4267 |
1.4267 |
|
C8-C9 |
1.4305 |
1.4467 |
1.4159 |
1.4159 |
|
C12-S19 |
1.7297 |
1.6856 |
1.7696 |
1.7696 |
|
C9-C11 |
1.411 |
1.444 |
1.4317 |
1.4317 |
|
C11-C23 |
1.4667 |
1.4823 |
1.4632 |
1.4632 |
|
C20-S19 |
1.7475 |
1.7292 |
1.8032 |
1.8032 |
|
Bond angles |
|
|
|
|
|
C23-C11-C9 |
121.7865 |
125.0063 |
123.7229 |
123.7229 |
|
N34-C11-C23 |
117.4414 |
114.1965 |
116.4952 |
116.4952 |
|
C11-C9-C8 |
119.6381 |
118.6039 |
118.4523 |
118.4523 |
|
N35-C12-N34 |
124.7318 |
122.7712 |
120.5005 |
120.5005 |
|
N34-C11-C9 |
120.7614 |
120.7959 |
119.7545 |
119.7545 |
|
C9-C8-N35 |
118.4099 |
117.212 |
118.7794 |
118.7794 |
|
C11-N34-C12 |
118.4808 |
120.2026 |
121.6223 |
121.6223 |
|
C11-C9-C10 |
125.0995 |
123.5077 |
122.6476 |
122.6476 |
|
N35-C12-S19 |
118.3799 |
115.3081 |
116.5717 |
116.5717 |
|
N34-C12-S19 |
116.8846 |
121.8403 |
122.8582 |
122.8582 |
|
Dihedral angles |
|
|
|
|
|
C9-C11-C23-C24 |
-52.9517 |
-83.9955 |
-51.7433 |
-51.7433 |
|
N34-C11-C23-C24 |
128.2285 |
96.4335 |
130.1701 |
130.1701 |
|
C9-C11-C23 -C25 |
128.0753 |
97.27 |
129.6316 |
129.6316 |
|
C23-C11-N34-C12 |
179.8251 |
-178.6317 |
-174.0151 |
-174.0151 |
|
C23-C11-C9 -C8 |
-177.7174 |
176.5349 |
174.3253 |
174.3253 |
|
N34-C11-C9 -C8 |
1.0637 |
-3.9206 |
-7.6472 |
-7.6472 |
|
C9-C11-N34 -C12 |
0.9926 |
1.7774 |
7.8181 |
7.8181 |
|
C9-C8-C35 -C12 |
11.478 |
7.9864 |
19.5368 |
19.5368 |
|
N34-C12-N35-C8 |
-10.0601 |
-10.7303 |
-19.968 |
-19.968 |
Compound 4
Table- 4
|
Parameters |
Compd 4 |
|
|
|
|
AM1 |
MNDO |
PM3 |
PM3MM |
|
|
Bond lenghts |
|
|
|
|
|
C12-N31 |
1.3386 |
1.3282 |
1.3336 |
1.3336 |
|
C11-N31 |
1.371 |
1.3761 |
1.3839 |
1.3839 |
|
C12-N32 |
1.4113 |
1.4124 |
1.4248 |
1.4248 |
|
C8-N32 |
1.4044 |
1.4194 |
1.4261 |
1.4261 |
|
C8-C9 |
1.4328 |
1.4467 |
1.4181 |
1.4181 |
|
C12-S19 |
1.7227 |
1.6856 |
1.7699 |
1.7699 |
|
C11-C9 |
1.4419 |
1.4439 |
1.434 |
1.434 |
|
C11-C20 |
1.4649 |
1.4823 |
1.4621 |
1.4621 |
|
Bond angles |
|
|
|
|
|
C20-C11-C9 |
121.3618 |
125.0006 |
125.8445 |
125.8445 |
|
N31-C11-C20 |
117.4693 |
114.1868 |
114.8524 |
114.8524 |
|
C11-C9-C8 |
118.3832 |
118.5889 |
118.469 |
118.469 |
|
N32-C12-N31 |
124.4928 |
122.7162 |
120.4585 |
120.4585 |
|
N31-C11-C9 |
121.1659 |
120.8111 |
119.3003 |
119.3003 |
|
C9-C8-N32 |
118.8723 |
117.2106 |
119.2002 |
119.2002 |
|
C11-N31-C12 |
118.7256 |
120.2276 |
122.3254 |
122.3254 |
|
C11-C9-C10 |
122.5722 |
123.5194 |
123.3774 |
123.3774 |
|
N32-C12-S19 |
114.3444 |
115.0631 |
116.5551 |
116.5551 |
|
N31-C12-S19 |
121.1374 |
122.1415 |
122.9194 |
122.9194 |
|
Dihedral angles |
|
|
|
|
|
C9-C11-C20-C21 |
51.8251 |
97.2571 |
41.5696 |
41.5696 |
|
N31-C11-C20-C21 |
-127.5421 |
-82.3055 |
-137.8224 |
-137.8224 |
|
C9-C11-C20-C22 |
-129.9205 |
-84.0077 |
-140.047 |
-140.047 |
|
C20-C11-N31-C12 |
177.756 |
-178.6343 |
-175.7189 |
-175.7189 |
|
C20-C11-C9-C8 |
-177.4573 |
176.5354 |
175.3482 |
175.3482 |
|
N31-C11-C9-C8 |
1.8866 |
-3.9292 |
-5.2845 |
-5.2845 |
|
C9-C11-N31-C12 |
-1.6125 |
1.783 |
4.8463 |
4.8463 |
|
C9-C8-N32-C12 |
7.4994 |
7.9837 |
17.327 |
17.327 |
|
N31-C12-N32-C8 |
-7.6557 |
-10.7248 |
-18.199 |
-18.199 |
Compound 5
Table- 5
|
Parameters |
Compd 5 |
|
|
|
|
AM1 |
MNDO |
PM3 |
PM3MM |
|
|
Bond lenghts |
|
|
|
|
|
C12-N31 |
1.3387 |
1.3281 |
1.3335 |
1.3335 |
|
C11-N31 |
1.371 |
1.3761 |
1.3839 |
1.3839 |
|
C12-N32 |
1.4114 |
1.4124 |
1.4248 |
1.4248 |
|
C8-N32 |
1.4044 |
1.4193 |
1.4261 |
1.4261 |
|
C8-C9 |
1.4328 |
1.4467 |
1.4181 |
1.4181 |
|
C12-S19 |
1.7228 |
1.6855 |
1.7701 |
1.7701 |
|
C11-C9 |
1.4419 |
1.4439 |
1.434 |
1.434 |
|
C11-C20 |
1.4649 |
1.4823 |
1.4621 |
1.4621 |
|
Bond angles |
|
|
|
|
|
C20-C11-C9 |
121.1705 |
125.0055 |
125.8576 |
125.8576 |
|
N31-C11-C20 |
117.4671 |
114.183 |
114.8419 |
114.8419 |
|
C11-C9-C8 |
118.3805 |
118.5891 |
118.4682 |
118.4682 |
|
N32-C12-N31 |
124.4882 |
122.709 |
120.4596 |
120.4596 |
|
N31-C11-C9 |
121.1705 |
120.81 |
119.2979 |
119.2979 |
|
C9-C8-N32 |
118.8728 |
117.2084 |
119.208 |
119.208 |
|
C11-N31-C12 |
118.725 |
120.2312 |
122.3361 |
122.3361 |
|
C11-C9-C10 |
122.5746 |
123.5183 |
123.3802 |
123.3802 |
|
N32-C12-S19 |
114.303 |
115.0443 |
116.5177 |
116.5177 |
|
N31-C12-S19 |
121.183 |
122.1693 |
122.952 |
122.952 |
|
Dihedral angles |
|
|
|
|
|
C9-C11-C20-C21 |
51.8464 |
97.2873 |
41.4877 |
41.4877 |
|
N31-C11-C20-C21 |
-127.5248 |
-82.2702 |
-137.9142 |
-137.9142 |
|
C9-C11-C20-C22 |
-129.8956 |
-83.9815 |
-140.1434 |
-140.1434 |
|
C20-C11-N31-C12 |
177.772 |
-178.6232 |
-175.7579 |
-175.7579 |
|
C20-C11-C9-C8 |
-177.4778 |
176.5275 |
175.3996 |
175.3996 |
|
N31-C11-C9-C8 |
1.8701 |
-3.9425 |
-5.2228 |
-5.2228 |
|
C9-C11-N31-C12 |
-1.6004 |
1.7989 |
4.7979 |
4.7979 |
|
C9-C8-N32-C12 |
7.5218 |
8.0012 |
17.2946 |
17.2946 |
|
N31-C12-N32-C8 |
-7.6837 |
-10.7402 |
-18.1498 |
-18.1498 |
Compound 6
Table- 6
|
Parameters |
Compd 6 |
|
|
|
|
AM1 |
MNDO |
PM3 |
PM3MM |
|
|
Bond lenghts |
|
|
|
|
|
C12-N33 |
1.3271 |
1.3283 |
1.3356 |
1.3356 |
|
C11-N33 |
1.3898 |
1.3758 |
1.3798 |
1.3798 |
|
C12-N34 |
1.4117 |
1.4124 |
1.4261 |
1.4261 |
|
C8-N34 |
1.4041 |
1.4187 |
1.4273 |
1.4273 |
|
C8-C9 |
1.4365 |
1.4465 |
1.4166 |
1.4166 |
|
C12-S19 |
1.7307 |
1.6857 |
1.7693 |
1.7694 |
|
C11-C9 |
1.4026 |
1.4439 |
1.4322 |
1.4322 |
|
C11-C22 |
1.4677 |
1.4827 |
1.4615 |
1.4616 |
|
S19-C20 |
1.774 |
1.7438 |
1.8312 |
1.8313 |
|
C20-C37 |
1.4781 |
1.5055 |
1.4875 |
1.4875 |
|
Bond angles |
|
|
|
|
|
C22-C11-C9 |
121.8772 |
124.8936 |
124.5441 |
124.5391 |
|
N33-C11-C22 |
117.2937 |
114.2029 |
115.8928 |
115.8936 |
|
C11-C9-C8 |
119.7072 |
118.5809 |
118.393 |
118.3928 |
|
N34-C12-N33 |
124.7898 |
122.7019 |
120.2451 |
120.2473 |
|
N33-C11-C9 |
120.8149 |
120.9034 |
119.5077 |
119.511 |
|
C9-C8-N34 |
117.9195 |
117.2044 |
118.9264 |
118.9257 |
|
C11-N33-C12 |
118.3208 |
120.2087 |
121.9862 |
121.9841 |
|
C11-C9-C10 |
124.8064 |
123.5344 |
122.7599 |
122.759 |
|
C12-S19-C20 |
107.4853 |
111.9696 |
105.9124 |
105.9067 |
|
C20-C37-C39 |
120.274 |
120.7852 |
120.0362 |
120.0388 |
|
C20-C37-C38 |
120.376 |
121.1215 |
120.4442 |
120.4435 |
|
N34-C12-S19 |
113.4991 |
114.7716 |
117.1506 |
117.1523 |
|
N33-C12-S19 |
121.6496 |
122.3291 |
122.5304 |
122.5264 |
|
Dihedral angles |
|
|
|
|
|
C9-C11-C22-C23 |
-56.0118 |
-92.5341 |
-47.7965 |
-47.8589 |
|
N33-C11-C22-C23 |
125.351 |
87.5703 |
134.9345 |
-134.8963 |
|
C9-C11-C22-C24 |
124.8916 |
88.6246 |
134.0068 |
-133.9467 |
|
C22-C11-N33-C12 |
-178.5359 |
-179.6689 |
-175.4692 |
-175.5173 |
|
C22-C11-C9-C8 |
-179.1151 |
177.6677 |
174.6098 |
174.6485 |
|
N33-C11-C9-C8 |
-0.5253 |
-2.4434 |
-8.2133 |
-8.1997 |
|
C9-C11-N33-C12 |
2.8116 |
0.431 |
7.1155 |
7.0905 |
|
C9-C8-N34-C12 |
12.1393 |
6.9857 |
19.2286 |
19.2287 |
|
N33-C12-N34-C8 |
-10.5597 |
-9.503 |
-20.8874 |
-20.8988 |
|
S19-C20-C37-C39 |
78.7907 |
66.7287 |
81.2616 |
81.2499 |
|
S19-C20-C37-C38 |
-102.2602 |
-114.6461 |
-100.2235 |
-100.246 |
3. ANTIBACTERIAL STUDIES:
3. 1 Micro-organisms:
Two different bacterial strains were collected as test organisms to check the antimicrobial activity of organic compounds. The microbial cultures were procured from the IMTECH, Chandigarh.
These seven indicator test bacteria were:
Strain MTCC No.
1. Pseudomonas fluorescence 103
2. Staphylococcus aureus 1740
The bacteria were sub cultured in nutrient agar medium and the culture of each bacterium was preserved on the same medium at 40 C. The cultures were sub cultured periodically on the same medium at 370 C ± 20C.
3. 2 Composition of nutrient agar medium (NA)
Components Amount
NaCl 8g
Peptone 5g
Beef extract 3g
Agar 15g
Distilled water 1 lt.
pH 7
3. 3 Procedure for making medium:
NaCl (8g), Peptone (5g) and Beef extract (3g) were mixed in distilled water and made the final volume 1lt. pH was adjusted to 7. Finally, agar-agar powder (15 g) was added.
3. 4 Preparation of inoculums:
One loopful of 24 h old culture of bacteria was inoculated into 50 ml nutrient broth in 50ml Erlenmeyer flasks. Flasks were kept on rotary shaker (100 rpm) at 370 C±20 C for 24h.
3. 5 Method used for antibacterial activities
The antibacterial activity was checked using well plate assay. The details are given below:
Stock solutions:
The stock solutions of extracts and antibiotics were prepared. The stock solutions (2 mg/ml) were diluted in alcohol (organic extracts), distilled water (aq. Extracts) and in slightly warm water (antibiotics) to the desired concentrations i. e. 1000, 700, 500, 300, 100 and 30 µg. Six different concentrations were tested for antimicrobial activity.
Well plate assay:
Nutrient agar medium plates were prepared by pouring approximately 15 ml nutrient agar into the sterilized plates. A lawn of test bacteria was made with 5 ml of the molten agar (450 C) inoculated with 1 ml of inoculum consisting of 106 cells/ml after proper mixing on cyclomixer. After solidification, wells from agar plates were punched out with a sterile borer of 8mm diameter. Six different concentrations i. e. 1000µg, 700µg, 500µg, 300µg, 100µg and 30µg of extracts were poured into the wells with the help of micropipette under sterilized conditions. DMSO was employed as control. The plates were then incubated at 370 C±20 C. The zone of inhibition (ZI) around the wells was measured in mm after 24h incubation.
3. 6 Antibiotics:
Standard antibacterial antibiotics were used along with the selected best antimicrobial organic extracts. The antibacterial efficacy of the most effective extracts was compared with those of existing standard antibacterial antibiotics. viz. Tetracycline and Chloramphenicol.
3. 7 COMPOUNDS TO BE TESTED FOR ANTI-BACTERIAL ACTIVITY:
The following compounds were evaluated for antibacterial activity.
1
2
3
4
5
6
7
8
9
10
11
12
3. 8 OBSERVATIONS:
The following observations were made during the anti-bacterial activities of above mentioned compounds. These compounds were screened for anti-bacterial activity against Staphylococcus aureus and Pseudomonas fluorescence. The concentration of the compounds taken was 500 µg/ml for this screening (Table 7).
Table 7 : Antibacterial activity
|
Compound |
Staphylococcus aureus |
Pseudomonas fluorescence |
|
1. |
----- |
----- |
|
2. |
----- |
----- |
|
3. |
+ |
----- |
|
4. |
----- |
----- |
|
5. |
----- |
----- |
|
6. |
+ |
----- |
|
7. |
+ |
----- |
|
8. |
+ |
----- |
|
9. |
----- |
----- |
|
10. |
----- |
----- |
|
11. |
----- |
----- |
|
12. |
+ |
+ |
‘+’ indicates that these compounds acted as antibacterial agents.
The compounds 1, 2, 4, 5, 9, 10, 11 didn’t show any antibacterial activity against both of these bacterial strains.
The compound 12 which have shown antibacterial activity against both of these bacterial strains, was tested for the Minimal Inhibitory Concentration (MIC) using different concentrations.
The zones of inhibition (mm) of the compound 12 are compared with those of the standard drugs Tetracycline and Chloramphenicol. For calculating the MIC value of compound 12, the whole procedure of testing antibacterial activity was repeated using different concentrations (Table 8 and 9).
Table 8: Bacterial Strain- Staphylococcus aureus
|
Concentrations of Compound 12 (µg) |
Zone of inhibition of compound 12 (mm) |
Zones of inhibition (mm) |
|
|
Tetracycline |
Chloramphenicol |
||
|
1000 |
43 |
----- |
------ |
|
700 |
31 |
----- |
------ |
|
500 |
23 |
49 |
40 |
|
300 |
13 |
25. 5 |
18 |
|
100 |
3. 10 |
12. 6 |
8. 0 |
|
30 |
----- |
5. 3 |
3. 0 |
Table 9: Bacterial Strain- Pseudomonas fluorescence
|
Concentrations Of Compound 12 (µg) |
Zone of inhibition of compound 12 (mm) |
Zones of inhibition (mm) |
|
|
Tetracycline |
Chloramphenicol |
||
|
1000 |
37 |
------ |
------ |
|
700 |
24 |
------ |
------ |
|
500 |
19 |
46 |
48 |
|
300 |
6. 0 |
23 |
23 |
|
100 |
1. 0 |
9. 1 |
11 |
|
30 |
-------- |
2. 1 |
5. 3 |
4. RESULTS AND DISCUSSIONS:
1. The compounds 1, 2, 4, 5, 9, 10, 11 are inactive against both of the bacterial strains taken. viz. Staphylococcus aureus and Pseudomonas fluorescence.
2. The compound 12 is active towards both of the bacterial strains.
3. The results show that all the Quinazolinethiones screened for antibacterial activity, the thiones in which hydroxyl group has been present in the 4-phenyl ring (i. e. compound 12) show an increase in the antibacterial action as compared to compound 3, which has only 4-methoxy group in phenyl ring.
4. Also, S-ethyl derivative (compound 12) is most potent as S-Ethyl moiety is present on the right side of the expected boat shaped structure. This again shows that we cannot ignore the structural details of right hand side.
5. The result 3and4 leads to the conclusion that the S-Me or S-Et derivatives synthesized from vanillin are much more potent than other derivatives against anti-bacterial activities. Thus, the stereochemistry between the aryl group and the dihydropyrimidine ring was found to be one of the factors having a pronounced effect on biological activity. It was proposed that in receptor bound conformation of DHPMs, the substituted aryl ring is positioned axially, perpendicular to, and bisecting the boat like dihydropyridine/ dihydropyrimidine ring with the 4-arylsubstituted Z adopting a synperiplanar (relative to C4-H) orientation. Also, it was verified from the results discussed, that right hand side cannot be neglected in receptor bound theory.
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Received on 22.10.2010 Modified on 06.11.2010
Accepted on 28.11.2010 © AJRC All right reserved
Asian J. Research Chem. 4(4): April 2011; Page 560-566