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Review
. 2018 Dec 12;10(1):26-40.
doi: 10.1039/c8md00425k. eCollection 2019 Jan 1.

Recent developments in compounds acting in the DNA minor groove

Adeyemi Rahman  1 , Patrick O'Sullivan  1 , Isabel Rozas  1
Affiliations
Review

Recent developments in compounds acting in the DNA minor groove

Adeyemi Rahman et al. Medchemcomm. .

Abstract

The macromolecule that carries genetic information, DNA, is considered as an exceptional target for diseases depending on cellular division of malignant cells (i.e. cancer), microbes (i.e. bacteria) or parasites (i.e. protozoa). To aim for a comprehensive review to cover all aspects related to DNA targeting would be an impossible task and, hence, the objective of the present review is to present, from a medicinal chemistry point of view, recent developments of compounds targeting the minor groove of DNA. Accordingly, we discuss the medicinal chemistry aspects of heterocyclic small-molecules binding the DNA minor groove, as novel anticancer, antibacterial and antiparasitic agents.

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Figures

Fig. 1
Fig. 1. Key DNA–drug interactions: intercalators, alkylators, cleaving agents and minor groove binders (MGB).
Fig. 2
Fig. 2. Examples of DNA targeting agents used in clinic: intercalator (doxorubicin), cross-linking (melphalan and cisplatin), methylating (procarbazine) and cleaving (bleomycin).
Fig. 3
Fig. 3. Examples of known DNA minor groove binders used in clinic: distamycin A, netropsin, CC-1065, pentamidine and furamidine.
Fig. 4
Fig. 4. Structure of (di)aryl amidine-like derivatives with anticancer activity.
Fig. 5
Fig. 5. Structure of Rozas' di-phenyl amidine-like derivatives with anticancer activity.
Fig. 6
Fig. 6. Different structural moieties identified in distamycin and structures of polyamides and distamycin derivatives: tallismustine, brostallicin, compound 8 prepared by Suckling and co-workers, compound 9 prepared by Dervan and co-workers and benzamide 10.
Fig. 7
Fig. 7. Structure of bis-benzimidazoles 11, trabectedin and the PBD anthramycin indicating the relevant atoms.
Fig. 8
Fig. 8. Structure of polyamides 12, 13a, b, and 14a–d, developed as MGBs with antimicrobial and antifungal activity.
Fig. 9
Fig. 9. Structure of berenil, bis-indoles 15 developed by Opperman et al., amidino hydrazones 16 and 17, as well as compounds 18.
Fig. 10
Fig. 10. Structures of furamidine derivatives 19, 20, 21 and 22.
Fig. 11
Fig. 11. Structures of guanidine and 2-aminoimidazoline derivatives 23, 24, 25, 26 and 27.
See this image and copyright information in PMC

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