N-5 alkylation of 3:4-benz-Δ-carboline is a requirement for renal vasodilation and inhibition of platelet aggregation in the rat

Medicinal Chemistry Research

Volumn 6, Issue 9, 1996, Pages 602-610

  Oyekan, A O ^a,c   Ablordeppey, Seth Y ^b  

^a UNIVERSITY OF THE WEST INDIES   (Trinidad and Tobago)

^b FLORIDA A AND M UNIVERSITY   (United States)

^c NEW YORK MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0000544419     PISSN: 10542523     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (13)

1. Dwuma-Badu, D., Ayim, J.S.K., Fiagbe, N.I.Y., Knapp, J.E., Schiff, Jr., D.L., Slatkin, D.J., 1978, Constituents of West African medicinal plants. Quindoline from Cryptolepis sanguinolenta, J. Pharm. Sci.., Vol. 67 (3), 433-434.
2. Clark, A.M., Hufford, C.D., Liu, S., Ablordeppey. S., 1989, Development of New Anticandidal Drugs, Pharm. Res., 6 (9), 512.
3. 2+. Gen. Pharmacol., 24, 461-469.
4. 2+. Gen. Pharmacol., 24, 461-469.
5. Oyekan, A.O., 1994, The role of endothelium and cGMP in the renal vasodilator response to cryptolepine in the rat. J. Cardiovasc. Pharmacol., 23: 602-611.
6. Holt, S. J., Petrow, V., 1946, Carbazoles, Carbolines, and Related Compounds. Part I. Quindoline Derivatives, J. Chem. Soc., 607-611; Holt, S. J.; and Petrow, V., 1946, Carbazoles, Carbolines, and Related Compounds. Part II. Transformations of some quaternary salts of Quindoline, J. Chem. Soc., 919-922.
7. Holt, S. J., Petrow, V., 1946, Carbazoles, Carbolines, and Related Compounds. Part I. Quindoline Derivatives, J. Chem. Soc., 607-611; Holt, S. J.; and Petrow, V., 1946, Carbazoles, Carbolines, and Related Compounds. Part II. Transformations of some quaternary salts of Quindoline, J. Chem. Soc., 919-922.
8. Fichter, F., Boehringer, F., 1906, Quindoline, Ber. Dtsch. Chem. Ges., 39, 3936-3940.
9. 13C-NMR assignments of cryptolepine, a 3:4-δ-carboline derivative of Cryptolepis sanguinolenta, Planta Medica, 56: 416-418.
10. Figure 1 is a representation of cryptolepine and quindoline obtained from the CSC Chem3D 2.0 molecular modeling package from Cambridge Scientific Computing, Inc. The initial structure of cryptolepine and quindoline were imported from ChemDraw. These structures were minimized by CS Chem3D's implementation of the molecular mechanics method of MM2. Both energy and structural error minimizations were used. The observed stuctures were consistent with those obtained from the more elaborate molecular modeling studies performed in Sybyl. These studies were performed on SGI Indigo R4000 workstation running the sybyl 6.0 software from Tripos Associates. The initial structure of quindoline was obtained by joining fragments of carbazole and benzene from the Sybyl library and modifying the atom types accordingly. This structure was minimized by Maximin II before being subjected to full geometric optimization by the semiimperical method of AM1 using Sybyl's implementation of MOPAC. The structure of quindoline was modified to obtain the starting geometries of the other alkylated products. The remaining four derivatives were treated in a similar manner to that of quindoline in order to obtain the final structures.
11. Spitzer, T.D, Crouch, R.C., Martin, G.E., Sharaf, M.H.M., Schiff, P.L., Jr. Tackie, A.N., Boye, G.L., 1991, Total assignment of the proton and carbon NMR spectra of the alkaloid quindoline-Utilization of HMQC-TOCSY to indirectly establish protonated carbon-protonated carbon connectivities. J. Heterocycl. Chem., 28(8), 2065-70.
12. Tackie, A.N., Sharaf, M.H.M., Schiff, P.L., Jr., Boye, G.L, Crouch, R.C., Martin, G.E., 1991, Assignment of the proton and carbon NMR spectra of the indoloquinoline alkaloid cryptolepine, J. Heterocycl. Chem., 28, 1429-1435.
13. 5 mp 252 - 253°C); Cryptolepine Hydrochloride, 276 - 278°C, (Free Base 167 - 168°C, Lit. 167 - 168°C); 5-Ethylquindoline Hydroiodide, 279 - 281°C; 5-Propylquindoline Hydroiodide, 263.1 - 263.6°C; 5-Benzylquindoline Hydrate, 237 - 239°C.