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  Table of Contents  
ORIGINAL ARTICLE
Year : 2011  |  Volume : 2  |  Issue : 2  |  Page : 62-68  

Insignificant anticancer activity of novel substituted pyrimidine derivatives


1 Vishveshwarya Institute of Medical Science Dadri, Gautambudh Nagar, Uttar Pradesh; NIMS University, Jaipur, Rajasthan, India
2 Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, Meerut, Uttar Pradesh, India
3 Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, Meerut, Uttar Pradesh; Uttarakhand Technical University, Dehradun, Uttarakhand, India
4 M.D. University, Rohtak, India

Date of Web Publication25-Nov-2011

Correspondence Address:
Rupesh Dudhe
Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, NH-58, Baghpat Bypass Crossing, Meerut, Uttar Pradesh - 250 005
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0976-9234.90213

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   Abstract 

Background: Pyrimidine and fused pyrimidine derivatives play an important role in therapeutic strategies. It is known to be most prominent structures found in nucleic acid, including uracil, thymine, cytosine, adenine, and guanine, which are fundamental building blocks for deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Materials and Methods: A series of 3-[2-amino-6-(substituted)-pyrimidin-4-yl]-6-(substituted)-2H-chromen-2-one derivatives were prepared by reacting salicylaldehyde with ethylacetoacetate in the presence of piperidine by Knoevenagel reaction as a starting material. The chemical structures were confirmed by means of FTIR (Fourier Transform InfraRed Spectrophotometer-8400S), 1H NMR, and elemental analysis. The data of these synthesized compounds were submitted to National Institute of Health, USA, under the drug discovery program of NCI (National Cancer Institute) and screened for anticancer activity at a single high dose (10−5 M) in full NCI 60 cell lines. Results: Unfortunately, the selected compounds have not shown any potent significant anticancer activity in the NCI 60 cell line screening. Conclusion: The compound (T2) found to be most efficient anticancer activity with selective influence on breast cancer cell lines, especially on MCF7 cell line with a growth percentage of 33.63.

Keywords: Anticancer, Claisen-Schmidt condensation, Knoevenagel reaction, pyrimidine


How to cite this article:
Chaudhary A, Sharma PK, Kashyap SJ, Gupta JK, Dudhe R, Verma P. Insignificant anticancer activity of novel substituted pyrimidine derivatives. J Pharm Negative Results 2011;2:62-8

How to cite this URL:
Chaudhary A, Sharma PK, Kashyap SJ, Gupta JK, Dudhe R, Verma P. Insignificant anticancer activity of novel substituted pyrimidine derivatives. J Pharm Negative Results [serial online] 2011 [cited 2019 Sep 17];2:62-8. Available from: http://www.pnrjournal.com/text.asp?2011/2/2/62/90213


   Introduction Top


About 13% deaths of human beings throughout the world are caused by cancer, which is characterized by uncontrolled cell growth, metastasis, and invasion. [1] Although the risk of cancer increases with age, people of all ages, even fetuses, can be affected by the disease. The most occurring fatal cancers are lung, stomach, liver, colon, and breast cancer. Therefore, continuous search for new anticancer agents should be an active work in the research field at various laboratories. Among potential anticancer agents, heterocyclic compounds represent an outstanding type of anticancer drug moiety. In this research work, we synthesized a series of substituted 3-(2-aminopyrimidin-4-yl)-2H-chromen-2-one derivatives. Pyrimidine and fused pyrimidine derivatives play an important role in the treatment of various diseases. It is one of the most prominent structures found in nucleic acid, including uracil, thymine, cytosine, adenine, and guanine, which are fundamental building blocks for deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Pyrimidine presents an interesting group of compounds many of which possess widespread pharmacologic properties, such a antimicrobial, [2] analgesic, antiviral, anti-inflammatory, [3] anti-HIV, [4] antitubercular, [5] antitumor, [6] antineoplastic, [7] antimalarial, [8] diuretic, [9] cardiovascular [10] agents, hypnotic drugs for the nervous system, [11] calcium-sensing receptor antagonists, [12] and also for antagonists of the human A 2A adenosine receptor. [13] Several drugs have been developed as anticancer agents which contain pyrimidine moieties, such as cladribine, clofarabine, capecitabine, cytarabine, fludarabine, gemcitabine, decitabine, [14] and floxuridine. [15] Due to the great potential of activities, we synthesized various substituted pyrimidine derivatives and the data of these synthesized compounds were submitted to National Institute of Health, USA, under the drug discovery program of NCI (National Cancer Institute). As per the protocol of NCI, among all the synthesized compounds after screening by NCI, 13 compounds of the series were selected and granted NSC codes: 753232-O, 753233-P, 753234-Q, 7532235-R, 753236-S, 753237-T, 753238-U, 753696-S, 753697-T, 753698-U, 753699-V, 753700-W, and 753701-X and screened for anticancer activity at a single high dose (10−5 M) in full NCI 60 cell lines.


   Materials and Methods Top


The synthesis of 3-[2-amino-6-(substituted)-pyrimidin-4-yl]-6-(substituted)-2H-chromen-2-one derivatives (T1-T10 and BT1-BT10) respectively, was described in Scheme 1 and physical data are presented in [Table 1]. The 3-acetyl coumarin (3) were prepared by reacting salicylaldehyde with ethylacetoacetate in the presence of piperidine by Knoevenagel reaction. In the next step, the treatment of 3-acetyl coumarin (3) with various aromatic aldehydes in the presence of piperidine gives S1-S10 and BS1-BS10, respectively, by Claisen-Schmidt condensation. Finally various pyrimidine derivatives (T1-T10 and BT1-BT10) were obtained by reaction of S1-S10 and BS1-BS10 with guanidine HCl in good yield. The compounds were recrystallized from ethanol. The purity of compounds was checked by TLC. Spectral data IR, 1 H NMR, and mass spectra of the synthesized compounds were recorded and found in full agreement with the proposed structures. The elemental analysis results were within ±0.4% of the theoretic values.
Table 1: Physical data of synthesized compounds


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Pharmacology screening

Pharmacological evaluation of the anticancer activity was performed on the compounds inconvertibly selected by National Institute of Health, Bethesda, USA, under the drug discovery program of NCI. All the finally synthesized 20 compounds have been registered on its website and from those only 13 compounds have been selected. All the selected compounds have been given a unique NCI number. [16]

Methodology of the in vitro cancer screening

The human tumor cell lines of the cancer screening panel are grown in RPMI 1640 medium containing 5% fetal bovine serum and 2 μL glutamine. The cells are inoculated into 96-well microtiter plates in 100 μL at plating densities ranging from 5000 to 40,000 cells/well depending on the doubling time of individual cell lines. After cell inoculation, the microtiter plates are incubated at 37°C in the presence of 5% CO 2 , 95% air, and 100% relative humidity for 24 h prior to addition of experimental drugs. After 24 h, two plates of each cell line are fixed in situ with TCA(Tricarboxylic Acid), to represent a measurement of the cell population for each cell line at the time of drug addition (Tz). Experimental drugs are solubilized in dimethyl sulfoxide at desired final maximum test concentration and stored frozen prior to use. At the time of drug addition, an aliquot of frozen concentrate is thawed and diluted to twice the desired final maximum test concentration with complete medium containing 50 μg/mL gentamicin. Additional four, 10-fold or log serial dilutions are made to provide a total of five drug concentrations plus control. Aliquots of 100 μL of these different drug dilutions are added to the appropriate microtiter wells already containing 100 μL of medium, resulting in the required final drug concentrations.



After the following drug addition, the plates are incubated for an additional 48 h at 37°C, 5% CO 2 , 95% air, and 100% relative humidity. For adherent cells, the assay is terminated by the addition of cold TCA. Cells are fixed in situ by the gentle addition of 50 μL of cold 50% (w/v) TCA (final concentration, 10% TCA) and incubated for 60 min at 4°C. The supernatant is discarded, and the plates are washed 5 times with tap water and air dried. Sulforhodamine B (SRB) solution (100 μL) at 0.4 % (w/v) in 1 % acetic acid is added to each well, and plates are incubated for 10 min at room temperature. After staining, unbound dye is removed by washing 5 times with 1% acetic acid and the plates are air dried. Bound stain is subsequently solubilized with 10 mM Trizma base, and the absorbance is read on an automated plate reader at a wavelength of 515 nm. For suspension cells, the methodology is the same except that the assay is terminated by fixing settled cells at the bottom of the wells by gently adding 50 μL of 80% TCA (final concentration, 16% TCA). Using the 7 absorbance measurements [time zero, (Tz), control growth (C), and test growth in the presence of drug at the 5 concentration levels (Ti)], the percentage growth is calculated at each of the drug concentrations levels. Percentage growth inhibition is calculated as:

[(Ti − Tz)/(C − Tz)] Χ 100 for concentrations for which Ti ≥ Tz

[(Ti − Tz)/Tz] Χ 100 for concentrations for which Ti < Tz.

Three dose response parameters are calculated for each experimental agent. Growth inhibition of 50% (GI50) is calculated from [(Ti − Tz)/(C − Tz)] Χ 100 = 50, which is the drug concentration resulting in a 50% reduction in the net protein increase (as measured by SRB staining) in control cells during the drug incubation. The drug concentration resulting in total growth inhibition (TGI) is calculated from Ti = Tz. The LC50 (concentration of drug resulting in a 50% reduction in the measured protein at the end of the drug treatment as compared to that at the beginning) indicating a net loss of cells following treatment is calculated from [(Ti − Tz)/Tz] Χ 100 = −50. Values are calculated for each of these three parameters if the level of activity is reached; however, if the effect is not reached or is exceeded, the value for that parameter is expressed as greater or less than the maximum or minimum concentration tested. The compounds that reduce the growth of any one of the cell lines by 32% or less are passed on for further evaluation in the full panel of 60 cell lines.

Experimental

All the reagents and solvents used were laboratory grade and obtained from the supplier (Sigma-Aldrich, company-3050 St. Louis,USA., CDH, New Delhi, and Rankem, Okhla, New Delhi) or recrystalized/redistilled as necessary. The melting points of the products were determined by open capillaries method and are uncorrected. I.R. Spectra (KBr) were recorded on FTIR Spectrophotometer (Shimadzu FTIR 84005, 4000-400 cm−1 ). 1 H NMR spectra were recorded on a JEOL AL300 FTNMR 300 MHz spectrometer in CDCl 3 using TMS as an internal standard, with 1 H resonance frequency of 300 MHz. Chemical shift values are expressed in δ ppm. The purity of compounds synthesized, commercial reagents used, and monitor of reaction was done by thin layer chromatography (TLC) plates (Silica gel G). Two solvent systems: Toluene:Ethyl acetate:Formic acid (5:4:1) and Benzene: Acetone (9:1) were used to run TLC. The visualization of spots on TLC plates was obtained under iodine chamber and UV light.

General procedure for synthesis of substituted 3-acetyl coumarin (3)


A mixture of substituted salicylaldehyde (1) (0.01 M) and ethyl acetoacetate (2) (0.01 M) in ethanol were taken in a round bottom flask. To this mixture few drops of piperidine were added and refluxed for 2-3 h. After completion of reaction, the content was poured on crushed ice. The precipitate obtained was filtered, dried, and recrystallized from ethanol.

General procedure synthesis of S1-S10 and BS1-BS10

Equimolar quantities of 7-substituted 3-acetyl coumarin (3) and different substituted benzaldehydes were refluxed in absolute ethanol using piperidine as a catalyst for 8-10 h. The solution mixture was concentrated and poured onto crushed ice. The compound so obtained was filtered, dried, and recrystallized from ethanol to get pure crystalline solid.

General procedure synthesis of T1-T10 and BT1-BT10

Each and every compound prepared above (S1-S10 and BS1-BS10) (0.01 M) are reacted with guanidine HCl (0.01 M) was refluxed in ethanol for 8-10 h. The content was evaporated to dryness and the product so obtained was washed with water repeatedly and recrystallized from ethanol.

3-(2-amino-6-(2-chlorophenyl)-pyrimidin-4-yl)-2H-chromen-2-one (T1): IR (KBr, cm−1 ): 3151.47 (N-H strech), 1666.38 (C=O), 1539.09 and 1384.79 (C-N strech), 1269.07 (C-O-C), 875.62 (C-N bend), 825.48 (NH 2 bend), 752.19 (C-Cl). 1 H NMR (CDCl 3 -d0, δ, ppm): 4.27(s, 2H, NH2 ), 6.93-7.63 (m, 10H, Ar-H). Elemental analysis: Calcd; C, 65.24; H, 3.46; O, 9.15.

3-(2-amino-6-(3-chlorophenyl)-pyrimidin-4-yl)-2H-chromen-2-one (T2): IR (KBr, cm -1 ): 3352.05 (N-H strech), 1635.52 (C=O), 1485.09 and 1380.94 (C-N strech), 1242.07 (C-O-C), 894.91 (C-N bend), 825.48 (NH 2 bend), 752.19 (C-Cl). 1 H NMR (CDCl 3 -d, δ, ppm): 4.25 (s, 2H, NH2 ), 6.92-7.36 (m, 10H, Ar-H). Elemental analysis: Calcd; C, 65.24; H, 3.46; O, 9.15.

3-(2-amino-6-(4-chlorophenyl)-pyrimidin-4-yl)-2H-chromen-2-one (T3): IR (KBr, cm -1 ): 3367.48 (N-H strech), 1662.52 (C=O), 1585.38 and 1384.79 (C-N strech), 1226.64 (C-O-C), 825.48 (NH 2 bend), 756.04 (C-Cl). 1 H NMR (CDCl 3 -d0, δ, ppm): 4.25 (s, 2H, NH2 ), 7.02-7.50 (m, 10H, Ar-H). Elemental analysis: Calcd; C, 65.24; H, 3.46; O, 9.15.

3-(2-amino-6-(2-bromophenyl)-pyrimidin-4-yl)-2H-chromen-2-one (T4): IR (KBr, cm -1 ): 3402.20 (N-H strech), 1674.10 (C=O), 1585.38 and 1384.79 (C-N strech), 1230.50 (C-O-C), 871.76 (C-N bend), 833.19 (NH 2 bend), 651.89 (C-Br). 1 H NMR (CDCl 3 -d, δ, ppm): 4.96 (s, 2H, NH2 ), 7.25-7.63 (m, 10H, Ar-H). Elemental analysis: Calcd; C, 57.89; H, 3.07; O, 8.12.

3-(2-amino-6-(3-bromophenyl)-pyrimidin-4-yl)-2H-chromen-2-one (T5): IR (KBr, cm -1 ): 3421.48 (N-H strech), 1654.81 (C=O), 1585.38 and 1384.79 (C-N strech), 1230.50 (C-O-C), 756.04 (NH 2 bend), 648.04 (C-Br) . 1 H NMR (CDCl 3 -d0, δ, ppm): 4.27 (s, 2H, NH 2 ), 6.93-7.63 (m, 10H, Ar-H) Elemental analysis: Calcd; C, 57.89; H, 3.07; O, 8.12.

3-(2-amino-6-(4-bromophenyl)-pyrimidin-4-yl)-2H-chromen-2-one (T6): IR (KBr, cm−1 ): 3348.19 (N-H strech), 1674.10 (C=O), 1585.38 and 1365.51 (C-N strech), 1230.50 (C-O-C), 821.62 (NH 2 bend), 648.04 (C-Br) . 1 H NMR (CDCl 3 -d, δ, ppm): 3.96 (s, 2H, NH2 ), 6.90-7.73 (m, 10H, Ar-H). Elemental analysis: Calcd; C, 57.89; H, 3.07; O, 8.12.

3-(2-amino-6-(2-methoxyphenyl)-pyrimidin-4-yl)-2H-cromen-2-one (T7): IR (KBr, cm -1 ): 3421.48 (N-H strech), 2839.02 (C-H strech of O-CH 3 ), 1635.52 (C=O), 1488.94 and 1384.79 (C-N strech), 1458.08 (CH 3 Umbrella mode), 1245.93 (C-O-C), 829.33 (C-N bend), 752.19 (NH 2 bend). 1 H NMR (CDCl 3 -d0, δ, ppm): 3.88 (s, 3H, CH3 ), 4.25 (s, 2H, NH 2 ), 6.92-8.00 (m, 10H, Ar-H) Elemental analysis: Calcd; C, 69.56; H, 4.38; O, 13.90.

3-(2-amino-6-(3-methoxyphenyl)-pyrimidin-4-yl)-2H-chromen-2-one (T8): IR (KBr, cm -1 ): 3413.77 (N-H strech), 2835.16 (C-H strech of O-CH 3 ), 1639.38 (C=O), 1585.38 and 1384.79 (C-N strech), 1454.23 (CH 3 Umbrella mode), 1261.36 (C-O-C), 756.04 (NH 2 bend). 1 H NMR (CDCl 3 -d, δ, ppm): 3.81 (s, 3H, CH3 ), 3.87 (s, 2H, NH 2 ), 6.86-7.25 (m, 10H, Ar-H). Elemental analysis: Calcd; C, 69.56; H, 4.38; O, 13.90.

3-(2-amino-6-(2,4-dichlorophenyl)-pyrimidin-4-yl)-2H-chromen-2-one (T9): IR (KBr, cm -1 ): 3452.34 (N-H strech), 1631.67 (C=O), 1473.51 and 1384.79 (C-N strech), 1230.50 (C-O-C), 821.62 (C-N bend), 756.04 (NH 2 bend), 621.04 (C-Cl). 1 H NMR (CDCl 3 -d0, δ, ppm): 4.26 (s, 2H, NH2 ), 6.90-7.48 (m, 8H, Ar-H), 7.86 (s, 1H, CH). Elemental analysis: Calcd; C, 59.39; H, 2.89; O, 8.33.

3-(2-amino-6-(2,6-dichlorophenyl)-pyrimidin-4-yl)-2H-chromen-2-one (T10): IR (KBr, cm -1 ): 3452.34 (N-H strech), 1674.10 (C=O), 1550.66 and 1384.79 (C-N strech), 1230.50 (C-O-C), 833.19 (C-N bend), 771.77 (NH 2 bend), 659.62 (C-Cl). 1 H NMR (CDCl 3 -d, δ, ppm): 4.48 (s, 2H, NH 2 ), 6.90-7.48 (m, 8H, Ar-H), 7.88 (s, 1H, CH). Elemental analysis: Calcd; C, 59.39; H, 2.89; O, 8.33.

3-(2-amino-6-(2-chlorophenyl)-pyrimidin-4-yl)-6-bromo-2H-chromen-2-one (BT1): IR (KBr, cm -1 ): 3151.47 (N-H strech), 1650.95 (C=O), 1596.95 and 1361.65 (C-N strech), 1249.79 (C-O-C), 894.91 (C-N bend), 817.76 (C-Cl), 759.90 (NH 2 bend), 659.61 (C-Br). 1 H NMR (CDCl 3 -d0, δ, ppm): 4.72 (s, 2H, NH2 ), 6.72-7.25 (m, 9H, Ar-H). Elemental analysis: Calcd; C, 53.24; H, 2.59; O, 7.46.

3-(2-amino-6-(3-chlorophenyl)-pyrimidin-4-yl)-6-bromo-2H-chromen-2-one (BT2): IR (KBr, cm -1 ): 3294.19 (N-H strech), 1654.81 (C=O), 1596.95 and 1253.64 (C-N strech), 1234.36 (C-O-C), 871.76 (C-N bend), 817.76 (C-Cl), 763.76 (NH 2 bend), 659.61 (C-Br). 1 H NMR (CDCl 3 - d, δ, ppm): 4.88 (s, 2H, NH 2 ), 6.84-7.25 (m, 9H, Ar-H). Elemental analysis: Calcd; C, 53.24; H, 2.59; O, 7.46.

3-(2-amino-6-(4-chlorophenyl)-pyrimidin-4-yl)-6-bromo-2H-chromen-2-one (BT3): IR (KBr, cm−1 ): 3340.48 (N-H strech), 1685.67 (C=O), 1593.09 and 1365.51 (C-N strech), 1238.21 (C-O-C), 871.76 (C-N bend), 817.76 (C-Cl), 756.04 (NH 2 bend), 628.75 (C-Br). 1 H NMR (CDCl 3 - d, δ, ppm): 4.88 (s, 2H, NH2 ), 6.90-7.48 (m, 9H, Ar-H). Elemental analysis: Calcd; C, 53.24; H, 2.59; O, 7.46.

3-(2-amino-6-(2-bromophenyl)-pyrimidin-4-yl)-6-bromo-2H-chromen-2-one (BT4): IR (KBr, cm -1 ): 3355.91 (N-H strech), 1654.81 (C=O), 1542.95 and 1365.51 (C-N strech), 1238.21 (C-O-C), 875.62 (C-N bend), 779.19 (NH 2 bend), 628.75 (C-Br). 1 H NMR (CDCl 3 - d, δ, ppm): 3.51 (s, 2H, NH 2 ), 6.90-7.60 (m, 9H, Ar-H). Elemental analysis: Calcd; C, 48.23/48.19; H, 2.34; O, 6.76.

3-(2-amino-6-(3-bromophenyl)-pyrimidin-4-yl)-6-bromo-2H-chromen-2-one (BT5): IR (KBr, cm -1 ): 3355.91 (N-H strech), 1654.81 (C=O), 1542.95 and 1373.22 (C-N strech), 1269.07 (C-O-C), 871.76 (C-N bend), 779.19 (NH 2 bend), 628.75 (C-Br). 1 H NMR (CDCl 3 - d, δ, ppm): 3.94 (s, 2H, NH2 ), 6.72-7.41 (m, 9H, Ar-H). Elemental analysis: Calcd; C, 48.23; H, 2.34; O, 6.76.

3-(2-amino-6-(4-bromophenyl)-pyrimidin-4-yl)-6-bromo-2H-chromen-2-one (BT6): IR (KBr, cm -1 ): 3417.63 (N-H strech), 1666.38 (C=O), 1577.66 and 1384.79 (C-N strech), 1234.36 (C-O-C), 871.76 (C-N bend), 759.90 (NH 2 bend), 628.75 (C-Br). 1 H NMR (CDCl 3 -d, δ, ppm): 3.51 (s, 2H, NH2 ), 6.92-7.52 (m, 9H, Ar-H). Elemental analysis: Calcd; C, 48.23; H, 2.34; O, 6.76.

3-(2-amino-6-(2-methoxyphenyl)-pyrimidin-4-yl)-6-bromo-2H-chromen-2-one (BT7): IR (KBr, cm−1 ): 3382.91 (N-H strech), 2835.16 (C-H strech of O-CH 3 ), 1670.24 (C=O), 1550.66 and 1384.79 (C-N strech), 1477.37 (CH 3 Umbrella mode), 1245.93 (C-O-C), 871.76 (C-N bend), 756.04 (NH 2 bend), 628.75 (C-Br). 1 H NMR (CDCl 3 -d, δ, ppm): 3.88 (s, 3H, CH3 ), 3.93 (s, 2H, NH 2 ), 6.90-7.60 (m, 9H, Ar-H). Elemental analysis: Calcd; C, 56.62; H, 3.33; O, 11.31.

3-(2-amino-6-(3-methoxyphenyl)-pyrimidin-4-yl)-6-bromo-2H-chromen-2-one (BT8): IR (KBr, cm−1 ): 3367.48 (N-H strech), 2935.46 (C-H strech of O-CH 3 ), 1666.38 (C=O), 1577.66 and 1384.79 (C-N strech), 1477.37 (CH 3 Umbrella mode), 1265.22 (C-O-C), 871.76 (C-N bend), 783.05 (NH 2 bend), 628.75 (C-Br). 1 H NMR (CDCl 3 -d, δ, ppm): 3.882 (s, 3H, CH3 ), 3.887 (s, 2H, NH 2 ), 6.92-7.73 (m, 9H, Ar-H). Elemental analysis: Calcd; C, 56.62; H, 3.33; O, 11.31.

3-(2-amino-6-(2,4-dichlorophenyl)pyrimidin-4-yl)-6-bromo-2H-chromen-2-one (BT9): IR (KBr, cm−1 ): 3417.63 (N-H strech), 1677.95 (C=O), 1589.23 and 1384.79 (C-N strech), 1234.36 (C-O-C), 867.91 (C-N bend), 817.76 (C-Cl), 775.33 (NH 2 bend), 628.75 (C-Br). 1 H NMR (CDCl 3 -d, δ, ppm): 5.22 (s, 2H, NH2 ), 6.93-7.42 (m, 7H, Ar-H), 7.97 (s, 1H, CH). Elemental analysis: Calcd; C, 49.28; H, 2.18; O, 6.91.

3-(2-amino-6-(2,6-dichlorophenyl)pyrimidin-4-yl)-6-bromo-2H-chromen-2-one (BT10): IR (KBr, cm−1 ): 3425.34 (N-H strech), 1604.66 (C=O), 1589.23 and 1384.79 (C-N strech), 1265.22 (C-O-C), 871.76 (C-N bend), 817.76 (C-Cl), 775.33 (NH 2 bend), 628.75 (C-Br). 1 H NMR (CDCl 3 -d, δ, ppm):5.18 (s, 2H, NH2 ), 6.72-7.41 (m, 7H, Ar-H), 7.94 (s, 1H, CH). Elemental analysis: Calcd; C, 49.28; H, 2.18; O, 6.91.


   Result and Disscusion Top


All the compounds submitted to the NCI 60 cell screen have been tested initially at a single high dose (10−5 M) in the full NCI 60 cell panel. The operation of this screen utilizes 60 different human tumor cell lines, representing leukemia, melanoma, and cancers of the lung, colon, brain, ovary, breast, prostate, and kidney. Only compounds which satisfy predetermined threshold inhibition criteria will progress to the 5-dose screen. Unfortunately the selected compounds have not shown any significant anticancer activity in the NCI 60 cell line screening and will not be processed further for 5-dose screen.

The mean growth percentage, range of growth percentage, and growth percentage relative to most sensitive cell line are depicted in [Table 2]. The tested compounds showed a broad spectrum of growth inhibitory activity against human tumor cells as well as distinctive patterns of selectivity [Figure 1]. Compound (T2) was found to be a highly sensitive cell breast cancer MCF7 with a growth percent of most sensitive cell line was −66.37, while least active over other cell line.
Table 2: Anticancer screening data of synthesized compounds


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Figure 1: Selected NCI 60 cell screening data highlighting the potency of compound T2 (NSC-753233-P)

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