CALANOLIDE A

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H26O5
Molecular Weight	370.4388
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCC1=CC(=O)OC2=C3[C@@H](O)[C@H](C)[C@@H](C)OC3=C4C=CC(C)(C)OC4=C12

InChI

InChIKey=NIDRYBLTWYFCFV-FMTVUPSXSA-N

InChI=1S/C22H26O5/c1-6-7-13-10-15(23)26-21-16(13)20-14(8-9-22(4,5)27-20)19-17(21)18(24)11(2)12(3)25-19/h8-12,18,24H,6-7H2,1-5H3/t11-,12-,18+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28769808 | https://www.ncbi.nlm.nih.gov/pubmed/15193138 | https://www.ncbi.nlm.nih.gov/pubmed/14980631

Calanolide A is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) originally extracted from a tropical tree (Calophyllum lanigerum) in the Malaysian rain forest. Viral life-cycle studies indicate that calanolide A acts early in the infection process, similar to the known HIV reverse transcriptase (RT) inhibitor 2', 3'-dideoxycytidine. In enzyme inhibition assays, calanolide A potently and selectively inhibits recombinant HIV type 1 RT but not cellular DNA polymerases or HIV type 2 RT within the concentration range tested. Phase I studies have found that calanolide A is well tolerated. Consequently, it has potential clinical applications in combination with other antiviral drugs to suppress HIV-1 mutants. Nevertheless, the development of calanolide A has been delayed due to its low therapeutic index (range: 16–279), non-ideal antiviral activity, and the complexity of its extraction from plants

Approval Year

PubMed

Title	Date	PubMed
The N137 and P140 amino acids in the p51 and the P95 amino acid in the p66 subunit of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase are instrumental to maintain catalytic activity and to design new classes of anti-HIV-1 drugs.	2005-04-25	15848161
HIV-1 inhibitory compounds from Calophyllum brasiliense leaves.	2004-09	15340243
New 3-O-acyl betulinic acids from Strychnos vanprukii Craib.	2004-06	15217281
Concise synthesis of anti-HIV-1 active (+)-inophyllum B and (+)-calanolide A by application of (-)-quinine-catalyzed intramolecular oxo-Michael addition.	2004-04-16	15074925
Anti-HIV natural product (+)-calanolide A is active against both drug-susceptible and drug-resistant strains of Mycobacterium tuberculosis.	2004-03-01	14980631
Safety and pharmacokinetic profile of multiple escalating doses of (+)-calanolide A, a naturally occurring nonnucleoside reverse transcriptase inhibitor, in healthy HIV-negative volunteers.	2002-12-26	12501127
Coumarins and pyranocoumarins, potential novel pharmacophores for inhibition of measles virus replication.	2002-01	12180648
Inhibition of HIV-1 reverse transcriptase and HIV-1 replication by Calophyllum coumarins and xanthones.	2002-01	11842340
Plant-derived and semi-synthetic calanolide compounds with in vitro activity against both human immunodeficiency virus type 1 and human cytomegalovirus.	2000-01	10693651
Unique anti-human immunodeficiency virus activities of the nonnucleoside reverse transcriptase inhibitors calanolide A, costatolide, and dihydrocostatolide.	1999-08	10428899
Sensitivity and resistance to (+)-calanolide A of wild-type and mutated forms of HIV-1 reverse transcriptase.	1999	10723499
Structural analogues of the calanolide anti-HIV agents. Modification of the trans-10,11-dimethyldihydropyran-12-ol ring (ring C).	1997-03-14	9083491
Antiviral activity and mechanism of action of calanolide A against the human immunodeficiency virus type-1.	1996-11	8930167
Structure-activity modifications of the HIV-1 inhibitors (+)-calanolide A and (-)-calanolide B.	1996-10-25	8893846
Synthesis, chromatographic resolution, and anti-human immunodeficiency virus activity of (+/-)-calanolide A and its enantiomers.	1996-03-15	8632437
Biological and biochemical anti-human immunodeficiency virus activity of UC 38, a new non-nucleoside reverse transcriptase inhibitor.	1996-01	8558446
Characteristics of a group of nonnucleoside reverse transcriptase inhibitors with structural diversity and potent anti-human immunodeficiency virus activity.	1995-10	7475321
Resistance to 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives is generated by mutations at multiple sites in the HIV-1 reverse transcriptase.	1995-06-20	7540784
Comparative anti-HIV evaluation of diverse HIV-1-specific reverse transcriptase inhibitor-resistant virus isolates demonstrates the existence of distinct phenotypic subgroups.	1995-03	7541618
Specific inhibition of the reverse transcriptase of human immunodeficiency virus type 1 and the chimeric enzymes of human immunodeficiency virus type 1 and type 2 by nonnucleoside inhibitors.	1993-05	7685994
Analysis of nonnucleoside drug-resistant variants of human immunodeficiency virus type 1 reverse transcriptase.	1993-04	7680393
The calanolides, a novel HIV-inhibitory class of coumarin derivatives from the tropical rainforest tree, Calophyllum lanigerum.	1992-07-24	1379639

Patents

Name

Type

Language

CALANOLIDE A

Common Name

English

NSC-650886

Preferred Name

English

(+)-(10R,11S,12S)-10,11-TRANS-DIHYDRO-12-HYDROXY-6,6,10,11-TETRAMETHYL-4-PROPYL-2H,6H-BENZO(1,2-B:3,4-B':5,6-B'')TRIPYRAN-2-ONE

Common Name

English

Code System Code Type Description

EPA CompTox

DTXSID601316787