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Details

Stereochemistry ABSOLUTE
Molecular Formula C24H40N2
Molecular Weight 356.5878
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 8
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CONESSINE

SMILES

[H][C@]12CC[C@@]3([H])[C@]4([H])CC=C5C[C@H](CC[C@]5(C)[C@@]4([H])CC[C@]13CN(C)[C@H]2C)N(C)C

InChI

InChIKey=GPLGAQQQNWMVMM-MYAJQUOBSA-N
InChI=1S/C24H40N2/c1-16-20-8-9-22-19-7-6-17-14-18(25(3)4)10-12-23(17,2)21(19)11-13-24(20,22)15-26(16)5/h6,16,18-22H,7-15H2,1-5H3/t16-,18-,19+,20+,21-,22-,23-,24-/m0/s1

HIDE SMILES / InChI

Molecular Formula C24H40N2
Molecular Weight 356.5878
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 8 / 8
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Conessine is a plant steroid alkaloid that acts as a potent and specific antagonist of histamine H3 receptors. Conessine displayed high affinity at both rat and human H3 receptors (pKi = 7.61 and 8.27) and generally high selectivity against other sites, including histamine receptors H1, H2, and H4. Conessine was found to efficiently penetrate the CNS and reach very high brain concentrations. Although the very slow CNS clearance and strong binding to adrenergic receptors discouraged focus on conessine itself for further development, its potency and novel steroid-based skeleton motivated further chemical investigation. Modification based on introducing diversity at the 3-nitrogen position generated a new series of H3 antagonists with higher in vitro potency, improved target selectivity, and more favorable drug-like properties. Conessine also has high affinity for the adrenergic receptors. Conessine has being shown to possess anti-malarial activity. In India conessine finds therapeutic use for treatment of dysentery and helminthic disorders.

CNS Activity

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
8.27 null [pKi]
6.18 null [pKi]
1.04 µM [IC50]
21.0 µM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
Mice: Conessine significantly reduced parasitaemia (at 10 mg/kg exhibited 88.95% parasite inhibition) in P. berghei-infected mice. Conessine was administered orally to mice of different groups for four days
Route of Administration: Oral
In Vitro Use Guide
Conessine showed in vitro anti-plasmodial activity with its IC₅₀ value 1.9 ug/ml and 1.3 ug/ml using schizont maturation and pLDH assay respectively. The compound showed cytotoxity IC₅₀= 14 ug/ml against L6 cells of rat skeletal muscle myoblast.
Substance Class Chemical
Record UNII
EZ38J9BBDF
Record Status Validated (UNII)
Record Version