RECENT PROGRESS IN CALOPHYLLUM COUMARINS AS POTENT ANTI-HIV AGENTS - Medicinal Chemistry of Bioactive Natural Products - page 332

TABLE 8-3. Activities of Calanolides Against Viruses Resistant to HIV-1-Specific Inhibitors

EC50 (mM) a

Drug(s) to Which Isolates
are Resistant (mutation) Nevirapine a AZT a ( þ )-Calanolide A ( )-Calanolide B ( )-Dihydrocalanolide B

IIIB (control) 0.1 0.2 0.2 0.01 0.05

Oxathiin carboxanilide (L100I) > 27 > 270 > 20 0.1 0.04

ND b UC10-costatolide (K103N) > 27 > 270 > 20 0.003

Thiazolobenzimidazole (V108I) 24.0 4.4 3.5 0.3 0.04

TIBO-R82150 (A98G-V108I) 22.0 1.6 5.1 0.6 0.05

Calanolide A (T139I) > 27 4.5 > 20 0.01 0.01

Diphenylsulfone (Y181C) 0.08 0.08 < 0.01 5.9 0.01

Nevirapine (Y181C) < 0.01 < 0.01 0.09 > 38 0.03

Pyridinone (Y181C-L103N) 0.12 0.8 0.8 > 38 0.01

E-BPTU(Y181C) 0.1 < 0.08 < 0.06 1.9 0.03

UC38(Y181C) 0.2 < 0.03 0.1 1.9 0.01

3TC(M184V) 0.3 1.3 1.0 0.01 0.02

Costatolide (Y188H) > 27 > 27 > 27 ND 0.004

HEPT (P236L) 0.6 1.1 0.2 0.02 0.01

a Nevirapine (NNRTI) and AZT (NRTI) are the positive control compounds.
b ND: not determined.