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Review
. 2023 Nov 7;15(11):2597.
doi: 10.3390/pharmaceutics15112597.

Bombesins: A New Frontier in Hybrid Compound Development

Pawel Serafin  1 , Patrycja Kleczkowska  1   2
Affiliations
Review

Bombesins: A New Frontier in Hybrid Compound Development

Pawel Serafin et al. Pharmaceutics. .

Abstract

Recently, bombesin (BN) and its analogs have attracted much attention as excellent anticancer agents because they interact with specific receptors widely distributed on the surface of various cancer cells. However, their biological properties proceed far beyond this, given a broad spectrum of activity. Bombesin receptor ligands are effective drugs for the treatment of rheumatoid arthritis or gastrointestinal diseases. However, most diseases are complex, and the use of polytherapy may lead to pharmacokinetic and pharmacodynamic drug-drug interactions, resulting in side effects. Therefore, there is a need to develop effective compounds that also contain BN or its analogs, which are combined with other structural entities, thus generating a so-called hybrid drug. Hybrid drugs that contain bombesin pharmacophore(s) may be proposed as a solution to the problem of polytherapy or the lack of an effective cure. Such structures have now demonstrated the desired efficacy, though information on these aforementioned compounds is relatively scarce. Therefore, our paper aims to encourage researchers to focus on bombesins. Herein, we indicate that the hybrid approach should also be firmly applied to bombesins and the BN receptor family. This paper's structure is divided into two main sections demonstrating bombesins and their properties, as well as recent data on bombesin-based hybrid compounds and their potential usefulness in medicine. Overall, it refers to the discovery and synthesis of modified bombesin-based hybrid compounds.

Keywords: biological properties; bombesin; bombesin receptors; efficacy; hybrid development.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Different types of molecular hybridization.
Figure 2
Figure 2
Examples of some of the clinically confirmed beneficial and deleterious biological effects of bombesins in humans.
Figure 3
Figure 3
Molecular targets (receptors) for the BN family; BB1—bombesin 1 receptor subtype (neuromedin B receptor), BB2—bombesin 2 receptor subtype (gastrin-releasing peptide (GRP) receptor), BB3—bombesin 3 receptor subtype, NK1—neurokinin 1 receptor, DRD1/DRD2—dopamine 1 receptor subtype and dopamine 2 receptor subtype, respectively.
Figure 4
Figure 4
Possible advantages and disadvantages of BN-based hybrid drugs. The red box indicates potential hybrid compositions, as C- or/and N-terminus can be replaced by BN or its analogs as well as other structures with a completely new molecular target.
Figure 5
Figure 5
Representative hybrid compound combining ago- and antagonist ligands at BN receptors designed by Kroll et al.
See this image and copyright information in PMC

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