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=C1C3=C(C=CC(C)(C)O3)C4=C2[C@@H](O)[C@H](C)[C@@H](C)O4

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 calanolides, a novel HIV-inhibitory class of coumarin derivatives from the tropical rainforest tree, Calophyllum lanigerum.	1992 Jul 24	1379639
Analysis of nonnucleoside drug-resistant variants of human immunodeficiency virus type 1 reverse transcriptase.	1993 Apr	7680393
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 May	7685994
Resistance to 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives is generated by mutations at multiple sites in the HIV-1 reverse transcriptase.	1995 Jun 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 Mar	7541618
Characteristics of a group of nonnucleoside reverse transcriptase inhibitors with structural diversity and potent anti-human immunodeficiency virus activity.	1995 Oct	7475321
Biological and biochemical anti-human immunodeficiency virus activity of UC 38, a new non-nucleoside reverse transcriptase inhibitor.	1996 Jan	8558446
Synthesis, chromatographic resolution, and anti-human immunodeficiency virus activity of (+/-)-calanolide A and its enantiomers.	1996 Mar 15	8632437
Antiviral activity and mechanism of action of calanolide A against the human immunodeficiency virus type-1.	1996 Nov	8930167
Structure-activity modifications of the HIV-1 inhibitors (+)-calanolide A and (-)-calanolide B.	1996 Oct 25	8893846
Structural analogues of the calanolide anti-HIV agents. Modification of the trans-10,11-dimethyldihydropyran-12-ol ring (ring C).	1997 Mar 14	9083491
Sensitivity and resistance to (+)-calanolide A of wild-type and mutated forms of HIV-1 reverse transcriptase.	1999	10723499
Unique anti-human immunodeficiency virus activities of the nonnucleoside reverse transcriptase inhibitors calanolide A, costatolide, and dihydrocostatolide.	1999 Aug	10428899
Plant-derived and semi-synthetic calanolide compounds with in vitro activity against both human immunodeficiency virus type 1 and human cytomegalovirus.	2000 Jan	10693651
Coumarins and pyranocoumarins, potential novel pharmacophores for inhibition of measles virus replication.	2002 Jan	12180648
Inhibition of HIV-1 reverse transcriptase and HIV-1 replication by Calophyllum coumarins and xanthones.	2002 Jan	11842340
Safety and pharmacokinetic profile of multiple escalating doses of (+)-calanolide A, a naturally occurring nonnucleoside reverse transcriptase inhibitor, in healthy HIV-negative volunteers.	2002 Nov-Dec	12501127
Concise synthesis of anti-HIV-1 active (+)-inophyllum B and (+)-calanolide A by application of (-)-quinine-catalyzed intramolecular oxo-Michael addition.	2004 Apr 16	15074925
New 3-O-acyl betulinic acids from Strychnos vanprukii Craib.	2004 Jun	15217281
Anti-HIV natural product (+)-calanolide A is active against both drug-susceptible and drug-resistant strains of Mycobacterium tuberculosis.	2004 Mar 1	14980631
HIV-1 inhibitory compounds from Calophyllum brasiliense leaves.	2004 Sep	15340243
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 Apr 25	15848161

Patents

Name

Type

Language

CALANOLIDE A

Common 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

NSC-650886

Code

English

Code System Code Type Description

EPA CompTox

DTXSID601316787