Synthesis, Characterization, Antimicrobial Activity and Anticancer of Some New Pyrazolo[1,5-a]pyrimidines and Pyrazolo[5,1-c]1,2,4-triazines
Authors: Hosny Mona A. , Zaki Yasser H. , Mokbel Wafaa A. , Abdelhamid Abdou O. 
Published: June 2019

Background:

Pyrazole and its derivatives are known to exhibit significant biological
and pharmacological activities such as anticancer, anti-inflammatory, antioxidant, antibacterial,
analgesic, antiviral, antimicrobial, antifungal, anti-glycemic, antiamoebic, and antidepressive.
Considering the immense biological properties, pyrazole is one of the most widely studied nitrogen-
containing heterocyclic nuclei. Fused pyrazole derivatives are composed of the pyrazole nucleus
attached to other heterocyclic moieties.

Objective:

The objective of this article is the synthesis of some new pyrazolo[1,5-a]pyrimidine and
pyrazolo[5,1-c]1,2,4-triazine derivatives with potential anticancer and antimicrobial activities.

Methods:

The in vitro growth inhibitory rates (%) and inhibitory growth activity (as measured by
IC50) of the newly synthesized compounds were determined against the MCF-7 human breast carcinoma
cell line in comparison with the well-known anticancer drug doxorubicin as the standard,
using the MTT viability assay. The data generated were used to plot a dose-response curve from
which the concentration (μM) of tested compounds required to kill 50% of the cell population
(IC50) was determined. Cytotoxic activity was expressed as the mean IC50 of three independent experiments.
The difference between inhibitory activities of all compounds with different concentrations
was statistically significant p < 0.001. All compounds were structurally characterized by different
spectroscopic techniques EI-MS, 1H-NMR, and 13C-NMR, and evaluated for their anticancer
and antimicrobial activities (antibacterial and antifungal).

Results:

Several pyrazolo[1,5-a]pyrimidine derivatives were synthesized from the reaction of 2-(4-
(5-amino-1H-pyrazol-3-yl)phenyl)-1H-indene-1,3(2H)-dione with the appropriate active methylene
compounds in boiling ethanol. Also, pyrazolo[5,1-c]triazines were obtained through the reaction
of 2-(4-(5-(chlorodiazenyl)-1H-pyrazol-3-yl)phenyl)-1H-indene-1,3(2H)-dione with various
active methylene compounds in ethanol containing sodium acetate at 0-5 °C. The structures of the
newly synthesized compounds were elucidated on the basis of elemental analysis, spectral data,
and alternative synthetic routes whenever possible. The newly synthesized compounds were evaluated
for their antitumor activity against a breast cancer cell line (MCF-7) and a human colon cancer
cell line (HCT-116). The results revealed that the tested compounds showed high variation in
the inhibitory growth rates and activities against the tested tumor cell lines. All newly synthesized
compounds screen towards microorganisms e.g. Gram-negative bacteria, Gram-positive bacteria,
and Fungi.

Conclusions:

2-(4-(5-Amino-1H-pyrazol-3-yl)phenyl)isoindoline-1,3-dione proved to be a useful
precursor for the synthesis of various pyrazolo[1,5-a]pyrimidine and pyrazolo[5,1-c]-1,2,4-
triazines. The structures of the newly synthesized compounds were confirmed by spectral data and
elemental analyses. The newly synthesized compounds were tested in vitro against the MCF-7,
HCT-116 human cancer cell line and compared with doxorubicin as the standard, using the MTT
viability assay. Most of the tested compounds were found to have moderate to high anticancer activity.