Hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives and evaluation of their anticancer and antimycobacterial activity

Figures & data

Scheme 1. Synthesis of hybrid imidazole (benzimidazole)/pyridine derivatives 2–6.

Scheme 2. Synthesis of hybrid Imz (Bimz)/quinoline derivatives 8–11.

Scheme 3. Design in the class of hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives.

Table 1. Percentage growth inhibition (PGI, μM)* data of compounds 2, 8, and 9 against an NCI 60 human tumor cell lines (selection)†.

Panel/cell line	Compound 2, PGI	Compound 8, PGI	Compound 9, PGI
Renal cancer
A498	76.38	71.32	52.92
UO-31	95.67	86.67	66.68
Breast cancer
MDA-MD-468	99.69	96.84	56.54
T-47D	95.02	84.83	66.49
CNS cancer
SF-295	101.52	102.13	66.68
Melanoma
SK-MEL-5	107.01	101.55	63.62
UACC-257	96.08	103.82	76.57
Leukemia
RPMI-8226	98.44	95.61	64.14
CCRF-CEM	103.51	102.28	70.70
K-562	96.39	101.22	79.72
SR	90.22	109.15	70.75
Non-small cell lung cancer
NCI-H23	104.67	95.31	69.62
A549/ATCC	89.85	103.65	77.74
Ovarian cancer
OVCAR-4	84.49	77.98	81.08
NCI/ADR-RES	105.73	105.83	75.91

Bold values indicate significant activity.

*The number reported for the one-dose assay, percentage growth inhibition (PGI), is growth relative to the no-drug control, and relative to the time zero number of cells.

† Full results are presented in the Supplementary Information.

Table 2. Solubility in microbiological medium and antimycobacterial activity of compounds 2, 3, 8, 9, and 11a–c against Mycobacterium tuberculosis H37Rv under aerobic conditions.

				Compound solubility
Compound	IC50 (μg/mL)	IC90 (μg/mL)	MIC (μM)	Starting concentration (μM)	Lowest insoluble concentration (μM)
2	>200	>200	>200	200	N/A
3	>200	>200	>200	200	N/A
8	>200	>200	>200	200	N/A
9	>200	77	>100	200	N/A
11a	>200	>200	>200	200	N/A
11b	>200	>200	>200	200	N/A
11c	>200	>200	>200	200	N/A
Control*
Rifampicin	0.0036	0.0061	0.0055	0.04	N/A

N/A means the compound was soluble at the highest concentration.

* Each experiment run included and other control compounds: metoprolol tartrate, phenytoin, haloperidol, simvastatin, diethylstilbestrol, and tamoxifen.