Synthesis of some dihydropyrimidine-based compounds bearing pyrazoline moiety and evaluation of their antiproliferative activity

Abstract

Two series of 2-(3,5-diaryl-4,5-dihydropyrazol-1-yl)-1-methyl-6-oxo-4-phenyl-1,6-dihydropyrimidine-5-carbonitriles 5a–h and 4-(4-chlorophenyl)-2-(3,5-diaryl-4,5-dihydropyrazol-1-yl)-1-methyl-6-oxo-1,6-dihydropyrimidine-5-carbonitriles 6a–h were synthesized via a cyclocondensation reaction of the corresponding 2-hydrazinopyrimidines 3a,b with the appropriate 2-propen-1-ones 4a–h. The target compounds were screened for their antiproliferative activity against A 549 (lung), HT 29 (colon), MCF 7 and MDA-MB 231 (breast) cell lines. The two most susceptible cell lines were the colon (HT 29) and breast (MDA-MB 231). Generally, the 4-unsubstitutedphenylpyrimidine derivatives 5a–h were more active than their 4-chlorophenylpyrimidine analogs 6a–h. Compounds 5e and 5g, showed high activity against three of the cell lines. The most active compound 5c possessed IC50 = 1.76 μM against A 549 cell line.

Synthesis and pharmacological evaluation of some new fluorine containing hydroxypyrazolines as potential anticancer and antioxidant agents

“…The crystal and instrumental parameters used in the unit cell determination, the data collection, and structure refinement parameters are presented in Table 2. The study of torsion angles asymmetric parameters and least-squares calculations of compound 4b reveals that the pyrazoline rings adopts an envelope conformation on C2 and its mean plane makes dihedral angles of 14.76(16) , 10.70 (17) and 80.49 (17) with the fluoromethoxyphenyl, methylphenyl and the dichlorophenyl rings respectively. In the compound 4c, the central pyrazoline ring adopts a twisted conformation on the C3eC2 bond and its mean plane make dihedral angles of 19.38(15) , 14.55 (16) and 82.07 (16) with the fluoromethoxyphenyl, methoxyphenyl and the dichlorophenyl rings respectively.…”

“…Among the nitrogen heterocycles, pyrazoline and their derivatives are acknowledged to possess a wide range of bioactivities [17]. Pyrazolines are used as anticancer [18,19], antioxidant [20], antitumor [21], anti-inflammatory [22], trypanocidal [23], MAO-B inhibitors [24], agonist of cannabinoid receptors [25] and antidepressant agents [26].…”

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“…Pyrimidine derivatives exhibited various biological activities such as anti-proliferative 24 , anticancer 25,26 , antihypertensive 27 , antioxidant 28,29 , antiviral 30 , antiinflammatory and analgesic activities 31,32 . Certain pyrimidine derivatives play a significant role in several biological processes and show, antileishmanial activities 33 and CNS depressant properties 34 .…”

Synthesis, Characterization and Pharmacological Activity of Novel 1-(3/-Substituted Phenyl-5/-Imino-Aryl Pyrimidine)-3-(Substituted Phenyl)-5-(Substituted Phenyl)-2-Pyrazoline Analogues

“…2-pyrazoline, five membered heterocyclic molecule with two adjacent nitrogen atoms possess a broad spectrum of biological activity such as antitumor 11 , antidepresent 12 , anti-epileptic 13 , anti-cancer 14 , analgesic 15 , antiproliferative 16 , anti-inflammatory 17 , anti-oxidant 18 , cytotoxic 19 and insecticidal 20 properties. The six membered heterocyclic molecule pyrimidine showed anti-viral 21 , anti-pyretic 22 , antihypertensive 23 , anti-proliferative 24 , anti-bacterial 25 , analgesic 26 and anti-nociceptive 27 effects. Many pyrimidine derivatives are reported to possess anti-malerial, anti-leishmanial 28 and CNS depressant properties 29 .…”