Synthesis and biological evaluation of new 3(2H)-pyridazinone derivatives as non-toxic anti-proliferative compounds against human colon carcinoma HCT116 cells

Figures & data

Figure 1. Structure-activity relationships (SARs) within the 3(2H)-pyridazinone derivatives reported in the literature.

Scheme 1. Synthesis of compounds VIa-o. Reagents and conditions: (i) AlCl₃, CS₂; (ii) H₂NNH₂, EtOH, reflux (6 h); (iii) Br₂, CH₃COOH, reflux (overnight); (iv) BrCH₂COOCH₂CH₃, K₂CO₃, acetone, reflux (overnight); (v) H₂NNH₂^.H₂O, MeOH, rt; (vi) EtOH, reflux (6 h), nonsubstituted/substitutedbenzaldehyde.

Table 1. Molecular structures, yields and melting points of VIa–o.

Compound	R1	R2	Yield (%)	mp (°C)
VIa	H	H	80	132
VIb	H	F	83	238
VIc	H	CF3	84	252
VId	CF3	H	68	222
VIe	CH3	H	96	210
VIf	OCH3	H	80	214
VIg	H	CH3	74	220
VIh	H	OCH3	85	207
VIi	H	NO2	38	265
VIj	H	i-C3H7	71	164
VIk	Br	H	89	189
VIl	F	H	72	224
VIm	H	Br	69	256
VIn	H	OH	42	251
VIo	Cl	Cl	91	229

Figure 2. Effects of serotonin (5-HT) in the range 10 pg/mL − 1 µg/mL on colon cancer HCT116 cell viability (MTT test). Data are means ± SE and analysed through analysis of variance (ANOVA), followed by post hoc Newman-Keuls test. ANOVA, p < 0.01; post hoc, *p < 0.05 vs. CTR (control) group.

Figure 3. Effects of compounds VIa–o at 10 µg/mL on serotonin (5-HT)-induced colon cancer HCT116 cell viability (MTT test). Data are means ± SE and analysed through analysis of variance (ANOVA), followed by post hoc Newman-Keuls test. ANOVA, p < 0.0001; post hoc, *p < 0.05, **p < 0.01, ***p < 0.001 vs. 5-HT (serotonin) group.

Figure 4. Effects of compounds VIa–o at 10 µg/mL on serotonin (5-HT)-induced reduction of kynurenic acid (KA) release from colon cancer HCT116 cells. Data are means ± SE and analysed through analysis of variance (ANOVA), followed by post hoc Newman-Keuls test. ANOVA, p < 0.0001; post hoc, *p < 0.05, **p < 0.01, ***p < 0.001 vs. 5-HT (serotonin) group.

Figure 5. Effects of compounds VIc, VIe, VIk and daunorubicin at 0.1–20 µg/mL on HCT116 cell viability. Data are means ± SE and analysed through analysis of variance (ANOVA), followed by post hoc Newman-Keuls test. ANOVA, p < 0.0001; post hoc, *p < 0.05, **p < 0.01, ***p < 0.001 vs CTR (control) group.

Figure 6. Effects of compounds VIe (3.09 µg/mL) and VIk (2.73 µg/mL) on the spontaneous migration of human colon cancer HCT116 cell line (wound healing paradigm). The spontaneous migration was monitored in the 48 h following treatment. Data are expressed as percentage scratch area relative to the untreated CTR group.