Evaluation of molecular descriptors for antitumor drugs with respect to noncovalent binding to DNA and antiproliferative activity

Table 1 Molecular descriptors for noncovalent DNA-binding drugs^a.

	NSC number	DNA binding	Mw	XlogP	HbD	HbA	PSA	Complexity	log Keq	Lipinski	GI₅₀
Actinomycin D	3053	Intercalation	1255	1.6	5	18	356	3030	5.38	2	8.7
Bleomycin	125066	Intercalation	1416	-1.9	20	30	627	2580	5.57	1	5.9
Chartreusin	5159	Intercalation	641	2.6	5	14	200	1150	5.45	2	5.7
Chromomycin	58514	minor-groove	1185	-0.6	8	26	359	2480	4.41	1	8.3
Daunorubicin	82151	intercalation	528	0.1	5	11	186	960	6.65	2	7.1
Distamycin A	82150	minor-groove	482	0.2	6	9	181	825	6.89	3	4.1
Doxorubicin	123127	intercalation	544	-0.5	6	12	206	977	6.30	1	7.2
Echinomycin	526417	bis-intercalation	1101	2.5	4	16	302	2200	5.52	2	8.1
Elsamicin A	369327	intercalation	654	2.9	5	14	206	1210	6.54	2	7.5
Epirubicin	256942	intercalation	544	-0.5	6	12	206	977	6.57	2	6.7
Ethidium	268986	intercalation	394	4.3	2	3	56	419	4.90	4	5.5
m-AMSA	249992	intercalation	394	3.8	2	6	80	601	4.30	4	6.2
Mitoxantrone	301739	intercalation	445	-3.1	8	10	163	571	6.78	3	7.2
Mithramycin A	24559	minor-groove	1085	-0.4	11	24	358	1940	5.08	1	7.9
Netropsin	3067	minor-groove	431	-1.7	7	10	211	723	6.40	2	4.0

^a Mw: Molecular weight, XlogP: partition coefficient that measures the differential solubility of a compound in two solvents, HbD: number of hydrogen bond donors in the structure, HbA: number of hydrogen bond acceptors, PSA: polar surface area (in Å²). Complexity: a rough estimate of how complicated a structure is. Both the elements contained and the displayed structural features including symmetry are considered. log Keq: logarithmic-transformed equilibrium binding constant for a drug-DNA complex (Keq in M^-1). Lipinski: Lipinski's score, the rule-of-five value used to measure bioavailability. GI₅₀ is used in place of -log(GI₅₀), the negative logarithm of the average drug concentration that inhibits cell growth in the NCI-60 cell lines (August 2008 data) as a measure of cytotoxicity or cytostasis.