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Review
. 2022 Oct;12(10):3783-3821.
doi: 10.1016/j.apsb.2022.05.020. Epub 2022 May 23.

Carbohydrate-based drugs launched during 2000 - 2021

Xin Cao  1 , Xiaojing Du  1 , Heng Jiao  1 , Quanlin An  1 , Ruoxue Chen  1 , Pengfei Fang  2 , Jing Wang  2 , Biao Yu  2
Affiliations
Review

Carbohydrate-based drugs launched during 2000 - 2021

Xin Cao et al. Acta Pharm Sin B. 2022 Oct.

Abstract

Carbohydrates are fundamental molecules involved in nearly all aspects of lives, such as being involved in formating the genetic and energy materials, supporting the structure of organisms, constituting invasion and host defense systems, and forming antibiotics secondary metabolites. The naturally occurring carbohydrates and their derivatives have been extensively studied as therapeutic agents for the treatment of various diseases. During 2000 to 2021, totally 54 carbohydrate-based drugs which contain carbohydrate moities as the major structural units have been approved as drugs or diagnostic agents. Here we provide a comprehensive review on the chemical structures, activities, and clinical trial results of these carbohydrate-based drugs, which are categorized by their indications into antiviral drugs, antibacterial/antiparasitic drugs, anticancer drugs, antidiabetics drugs, cardiovascular drugs, nervous system drugs, and other agents.

Keywords: Antibiotics; Anticancer drug; Antivirus drug; Carbohydrate-based drug; Glycoconjugate; Glycodrug.

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Figures

Image 1
Graphical abstract
Figure 1
Figure 1
The chemical structures of carbohydrate-based drugs launched during 2000–2021.
Figure 1
Figure 1
The chemical structures of carbohydrate-based drugs launched during 2000–2021.
Figure 2
Figure 2
Statistics of carbohydrate-based drugs by launched year (A) and their medical indications (B).
Figure 3
Figure 3
Statistics of the carbohydrate-based drugs according to chemical sources (A) and indications (B).
Figure 4
Figure 4
Carbohydrate-based drugs for COVID-19. (A) From AMP (55) to remdesivir (1) and its mode of action. RdRp, RNA-dependent RNA polymerase. (B) The potential antiviral nucleosides (2 and 3) for COVID-19 therapy and their parent compounds (58 and 59).
Figure 5
Figure 5
The antivires drugs (4–8) are derived from natural nucleoside and nucleotide 64–67.
Figure 6
Figure 6
The structure of other carbohydrate-based antiviral drugs. (A) From sialic acid (68) to the anti-influenza drugs launched before and after 2000–2021. (B) The red seaweed (Chondrus crispus) sourced carragelose (11).
Figure 7
Figure 7
The representative first-, second- and third-generation macrolide glycoside antibiotics.
Figure 8
Figure 8
Launched 16- and 18-membered macrolide glycoside antibiotic. (A) The macrolide glycoside antibiotic carrimycin (14) derived from spiramycin I (73). (B) Macrolide glycoside fidaxomicin (15).
Figure 9
Figure 9
The lipopeptide glycoside antibiotics developed during 2000–2021.
Figure 10
Figure 10
Aminoglycoside antibiotics antiparasitic drugs. (A) Antibacterial aminoglycoside plazomicin (19) derived from sisomicin (79). (B) The antileishmanicidal drug paromomycin (20) and amphotericin B (80).
Figure 11
Figure 11
The anticancer nucleosides azacitidine (21) and decitabine (22) derived from cytidines (81) and 2′-deoxycytidine (59).
Figure 12
Figure 12
Carbohydrate-based antineoplastic nucleosides and nucleotides. (A) The metabolism and resultant toxicity of fludarabine (83). (B) The anticancer nucleoside clofarabine (23) derived from 2′-deoxyadenosine (86). (C) The in vivo metabolism of nelarabine (24). (D) The anticancer nucleoside forodesine (25) which increase the plasma 2′-deoxyguanosine (91).
Figure 13
Figure 13
Other carbohydrate-based chemotherapy drugs. (A) The representative anthracycline anticancer drugs (92 and 93) and a active metabolit (94) of amrubicin (26). (B) The anticancer drug midostaurin (27) derived from staurosporine (95). (C) The immunomodulator anticancer drug mifamurtide (28) derived from MDP (96).
Figure 14
Figure 14
The action mechanism of SGLT1/2 inhibitors. (A) The glucose reabsorption mechanism of SGLT1/2 in renal tubule. (B) The SGLT2 inhibitory natural glycoside phlorizin (104), an active derivative T-1095 (105), and its metabolite T-1095A (106).
Figure 15
Figure 15
Chemical structure of SGLT1/2 inhibitors. (A) C-Glucoside SGLT2 inhibitors (29–32) launched during 2000–2021. (B) SGLT1/2 inhibitors bearing modified glucose units (33–37) launched during 2000–2021.
Figure 16
Figure 16
Launched second and third generation heparin products. (A) The low-molecular-weight heparin tinzaparin sodium (38) derived from natural heparin. (B) The synthetic heparin pentasaccharide fondaparinux (39).
Figure 17
Figure 17
The antiplatelet drugs ticagrelor (40) and cangrelor (41) derived from ADP (108) and ATP (109).
Figure 18
Figure 18
Carbohydrate-based nervous system drugs. (A) The AD drug sodium oligomannate (42) derived from brown algae β-d-(1,4)-polymannuranate (110). (B) Sugammadex (43) developed from cyclodextrin (111).
Figure 19
Figure 19
Carbohydrate-based drugs for other diseases. (A) Diquafosol tetrasodium (44) derived from UDP (112). (B) Lactitol (45) derived from lactose (113). (C) Magnesium isoglycyrrhizinate (46) prepared from licorice. (D) Miglustat (47) and migalastat (48) derived from 1-deoxynojirimycin (101). (E) Uridine triacetate (49) derived from uridine (114). (F) Regadenson (50) derived from adenosine (67).
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