TOTAROL

Possibly Marketed Outside US

First approved in 2015

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H30O
Molecular Weight	286.4516
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CCC3=C(C=CC(O)=C3C(C)C)[C@@]1(C)CCCC2(C)C

InChI

InChIKey=ZRVDANDJSTYELM-FXAWDEMLSA-N

InChI=1S/C20H30O/c1-13(2)18-14-7-10-17-19(3,4)11-6-12-20(17,5)15(14)8-9-16(18)21/h8-9,13,17,21H,6-7,10-12H2,1-5H3/t17-,20+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C20H30O
Molecular Weight	286.4516
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19067375 | https://www.ncbi.nlm.nih.gov/pubmed/17664318 | https://www.ncbi.nlm.nih.gov/pubmed/17348691
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19755141

Totarol is a meroterpene, and more precisely a terpenophenolic, a chemical compound that is part terpene and part natural phenol. It is a naturally produced diterpene that is bioactive as (+)-totarol. It was first isolated by McDowell and Esterfield from the heartwood of Podocarpus totara, a yew tree found in New Zealand. Totarol showed good activity against Mycobacterium tuberculosis H(37)Rv (MIC of 73.7 uM). It was also most active against the isoniazid-, streptomycin-, and moxifloxacin-resistant variants (MIC of 38.4, 83.4 and 60 uM, respectively). Totarol demonstrated nematicidal and antifouling activities against Caenorhabditis elegans and Artemia salina, it inhibited Leishmania donovani promastigotes, showed good antimicrobial activity against effluxing strains of Staphylococcus aureus. Totarol inhibits bacterial proliferation by targeting FtsZ and it may be useful as a lead compound to develop an effective antitubercular drug.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Staphylococcus aureus 67 Target ID: CHEMBL352 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26193949 \| https://www.ncbi.nlm.nih.gov/pubmed/17664318	Inhibitor 8297
Plasmodium falciparum (isolate K1 / Thailand) 8 Target ID: CHEMBL612856 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22196513	Inhibitor 8297	11.69 µM [IC50]
Mycobacterium tuberculosis H37Rv 11 Target ID: CHEMBL2111188 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19755141	Inhibitor 8297
Leishmania donovani 13 Target ID: CHEMBL367 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19067375	Inhibitor 8297
Cell division protein FtsZ 1 Target ID: CHEMBL4213 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17348691	Inhibitor 8297	11.0 µM [Kd]

Conditions

Condition	Modality	Highest Phase	Product
Malaria 95 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22196513	Curative	Basic research	Unknown Approved Use Unknown
Tuberculosis 83 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19755141	Curative	Basic research	Unknown Approved Use Unknown
Leishmaniasis 20 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19067375	Curative	Basic research	Unknown Approved Use Unknown
Staphylococcus aureus infection 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26193949 https://www.ncbi.nlm.nih.gov/pubmed/17664318	Curative	Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
A cyclic peroxide of clerodenoic acid from the Taiwanese liverwort Schistochila acuminata.	2001	11491401
Effects of (+)-totarol, a diterpenoid antibacterial agent, on phospholipid model membranes.	2001 Apr 2	11286971
Anti-tumor promoting diterpenes from the stem bark of Thuja standishii (Cupressaceae).	2001 Jul	11425594
Development of a method to quantify in vitro the synergistic activity of "natural" antimicrobials.	2003 Aug 25	12878383
Novel domino reactions for diterpene synthesis.	2004 Dec 10	15575777
Antimycobacterial constituents from Juniperus procera, Ferula communis and Plumbago zeylanica and their in vitro synergistic activity with isonicotinic acid hydrazide.	2004 Nov	15597311
Antineoplastic agents. 529. Isolation and structure of nootkastatins 1 and 2 from the Alaskan yellow cedar Chamaecyparis nootkatensis.	2004 Sep	15387645
Antifibrotic activity of diterpenes from Biota orientalis leaves on hepatic stellate cells.	2008 Jul	18704328

Patents

Sample Use Guides

In Vivo Use Guide

Rats were intravenously treated with totarol at 2 h, 4 h and 6 h after ischemia onset. Animals were randomly divided into six groups (n = 8–12 per group): Sham, Vehicle, totarol (0.1 ug/kg), totarol (1 ug/kg), totarol (10 ug/kg)

Route of Administration: Intravenous

In Vitro Use Guide

Totarol demonstrated nematicidal and antifouling activities against Caenorhabditis elegans and Artemia salina at a concentration of 80 ug/mL and 1 ug/mL, respectively.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 01:28:44 GMT 2023` Edited by `admin` on `Sat Dec 16 01:28:44 GMT 2023`
Record UNII	67NH2854WW
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TOTAROL

Official Name

English

(4BS-TRANS)-4B,5,6,7,8,8A,9,10-OCTAHYDRO-4B,8,8-TRIMETHYL-1-(1-ISOPROPYL)-2-PHENANTHRENOL

Common Name

English

(4AS,10AS)-7-HYDROXY-8-ISOPROPYL-1,1,4A-TRIMETHYL-1,2,3,4,4A,9,10,10A-OCTAHYDROPHENANTHRENE

Common Name

English

2-PHENANTHRENOL, 4B,5,6,7,8,8A,9,10-OCTAHYDRO-4B,8,8-TRIMETHYL-1-(1-METHYLETHYL)-, (4BS-TRANS)-

Common Name

English

2-PHENANTHRENOL, 4B,5,6,7,8,8A,9,10-OCTAHYDRO-4B,8,8-TRIMETHYL-1-(1-METHYLETHYL)-, (4BS,8AS)-

Common Name

English

NSC-299936

Code

English

(+)-TOTAROL

Common Name

English

TOTAROL [INCI]

Common Name

English

TRANS-TOTAROL

Common Name

English

PODOCARPA-8,11,13-TRIEN-13-OL, 14-ISOPROPY

Common Name

English

Code System Code Type Description

DAILYMED

67NH2854WW