Antineoplastic agents 397: Isolation and structure of sesterstatins 4 and 5 from Hyrtios erecta (The Republic of Maldives)

George Pettit; Rui Tan; Noeleen Melody; Zbigniew Cichacz; Delbert L. Herald; Michael S. Hoard; Robin Pettit; Jean Chapuis

doi:10.1016/S0960-894X(98)00373-4

Antineoplastic agents 397: Isolation and structure of sesterstatins 4 and 5 from Hyrtios erecta (The Republic of Maldives)

George Pettit, Rui Tan, Noeleen Melody, Zbigniew Cichacz, Delbert L. Herald, Michael S. Hoard, Robin Pettit, Jean Chapuis

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

Abstract

The wide ranging marine sponge Hyrtios erecta is the source of the spongistatins, a new class of macrocyclic lactone antineoplastic agents. Continuation of a detailed investigation of cancer cell growth inhibitory (P388 lymphocytic leukemia) fractions (trace) from H. erecta has revealed the presence (10^-5 to 10^-7% yield) of cytotoxic pentacyclic sesterterpenes. Employing P388 leukemia and human tumor cell line-guided bioassay techniques, two new moderate inhibitors of cancer cells were isolated and named sesterstatins 4 (1a, P388 ED₅₀ 4.9 μg/mL) and 5 (1b, DU-145 prostate GI₅₀ 1.9 μg/mL). Similar to other sesterterpenes, sesterstatin 5 inhibited growth of a Gram-positive bacterium. High field (500 MHz) 2-D NMR techniques were primarily employed for initial structural assignments, and structural assignments were confirmed by X-ray crystal structure determination of sesterstatin 4 (1a) and 5 (1b).

Original language	English (US)
Pages (from-to)	2093-2098
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	8
Issue number	16
DOIs	https://doi.org/10.1016/S0960-894X(98)00373-4
State	Published - Aug 18 1998

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/S0960-894X(98)00373-4

Cite this

@article{5df19a8a92344bebbe79ae2038c038ad,

title = "Antineoplastic agents 397: Isolation and structure of sesterstatins 4 and 5 from Hyrtios erecta (The Republic of Maldives)",

abstract = "The wide ranging marine sponge Hyrtios erecta is the source of the spongistatins, a new class of macrocyclic lactone antineoplastic agents. Continuation of a detailed investigation of cancer cell growth inhibitory (P388 lymphocytic leukemia) fractions (trace) from H. erecta has revealed the presence (10-5 to 10-7% yield) of cytotoxic pentacyclic sesterterpenes. Employing P388 leukemia and human tumor cell line-guided bioassay techniques, two new moderate inhibitors of cancer cells were isolated and named sesterstatins 4 (1a, P388 ED50 4.9 μg/mL) and 5 (1b, DU-145 prostate GI50 1.9 μg/mL). Similar to other sesterterpenes, sesterstatin 5 inhibited growth of a Gram-positive bacterium. High field (500 MHz) 2-D NMR techniques were primarily employed for initial structural assignments, and structural assignments were confirmed by X-ray crystal structure determination of sesterstatin 4 (1a) and 5 (1b).",

author = "George Pettit and Rui Tan and Noeleen Melody and Zbigniew Cichacz and Herald, {Delbert L.} and Hoard, {Michael S.} and Robin Pettit and Jean Chapuis",

note = "Funding Information: Acknowledgment. We are pleased to acknowledge the financial assistance provided by Outstanding Investigator Grant CA44344-01-09 awarded by the Division of Cancer Treatment Diagnosis and Centers, NCI, DHHS, the Arizona Disease Control Research Commission, the Farmie E. Rippel Foundation, the Robert B. Dalton Endowment Fund, Gary L. and Diane Tooker, Dr. John C. Budzinski, and John and Edith Reyno. For other helpful assistance, we thank the Government of the Republic ofMaldives (Maizan H. Maniku, A. Naseer, and M. Shiham), Drs. Michael D. W'dliams, Fiona Hogan, Jean M. Schmidt, Mr. David Carnell, and Mr. Lee Williams, the U.S. National Science Foundation (Grant Nos. BBS 88-04992 and CHE-8409644), and the NSF Regional Instrumentation Facility in Nebraska (Grant CHE-8620177).",

year = "1998",

month = aug,

day = "18",

doi = "10.1016/S0960-894X(98)00373-4",

language = "English (US)",

volume = "8",

pages = "2093--2098",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "16",

}

TY - JOUR

T1 - Antineoplastic agents 397

T2 - Isolation and structure of sesterstatins 4 and 5 from Hyrtios erecta (The Republic of Maldives)

AU - Pettit, George

AU - Tan, Rui

AU - Melody, Noeleen

AU - Cichacz, Zbigniew

AU - Herald, Delbert L.

AU - Hoard, Michael S.

AU - Pettit, Robin

AU - Chapuis, Jean

N1 - Funding Information: Acknowledgment. We are pleased to acknowledge the financial assistance provided by Outstanding Investigator Grant CA44344-01-09 awarded by the Division of Cancer Treatment Diagnosis and Centers, NCI, DHHS, the Arizona Disease Control Research Commission, the Farmie E. Rippel Foundation, the Robert B. Dalton Endowment Fund, Gary L. and Diane Tooker, Dr. John C. Budzinski, and John and Edith Reyno. For other helpful assistance, we thank the Government of the Republic ofMaldives (Maizan H. Maniku, A. Naseer, and M. Shiham), Drs. Michael D. W'dliams, Fiona Hogan, Jean M. Schmidt, Mr. David Carnell, and Mr. Lee Williams, the U.S. National Science Foundation (Grant Nos. BBS 88-04992 and CHE-8409644), and the NSF Regional Instrumentation Facility in Nebraska (Grant CHE-8620177).

PY - 1998/8/18

Y1 - 1998/8/18

N2 - The wide ranging marine sponge Hyrtios erecta is the source of the spongistatins, a new class of macrocyclic lactone antineoplastic agents. Continuation of a detailed investigation of cancer cell growth inhibitory (P388 lymphocytic leukemia) fractions (trace) from H. erecta has revealed the presence (10-5 to 10-7% yield) of cytotoxic pentacyclic sesterterpenes. Employing P388 leukemia and human tumor cell line-guided bioassay techniques, two new moderate inhibitors of cancer cells were isolated and named sesterstatins 4 (1a, P388 ED50 4.9 μg/mL) and 5 (1b, DU-145 prostate GI50 1.9 μg/mL). Similar to other sesterterpenes, sesterstatin 5 inhibited growth of a Gram-positive bacterium. High field (500 MHz) 2-D NMR techniques were primarily employed for initial structural assignments, and structural assignments were confirmed by X-ray crystal structure determination of sesterstatin 4 (1a) and 5 (1b).

AB - The wide ranging marine sponge Hyrtios erecta is the source of the spongistatins, a new class of macrocyclic lactone antineoplastic agents. Continuation of a detailed investigation of cancer cell growth inhibitory (P388 lymphocytic leukemia) fractions (trace) from H. erecta has revealed the presence (10-5 to 10-7% yield) of cytotoxic pentacyclic sesterterpenes. Employing P388 leukemia and human tumor cell line-guided bioassay techniques, two new moderate inhibitors of cancer cells were isolated and named sesterstatins 4 (1a, P388 ED50 4.9 μg/mL) and 5 (1b, DU-145 prostate GI50 1.9 μg/mL). Similar to other sesterterpenes, sesterstatin 5 inhibited growth of a Gram-positive bacterium. High field (500 MHz) 2-D NMR techniques were primarily employed for initial structural assignments, and structural assignments were confirmed by X-ray crystal structure determination of sesterstatin 4 (1a) and 5 (1b).

UR - http://www.scopus.com/inward/record.url?scp=0032544174&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032544174&partnerID=8YFLogxK

U2 - 10.1016/S0960-894X(98)00373-4

DO - 10.1016/S0960-894X(98)00373-4

M3 - Article

C2 - 9873492

AN - SCOPUS:0032544174

SN - 0960-894X

VL - 8

SP - 2093

EP - 2098

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 16

ER -

Antineoplastic agents 397: Isolation and structure of sesterstatins 4 and 5 from Hyrtios erecta (The Republic of Maldives)

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

CCDC 145736: Experimental Crystal Structure Determination

CCDC 145737: Experimental Crystal Structure Determination

Cite this

Antineoplastic agents 397: Isolation and structure of sesterstatins 4 and 5 from Hyrtios erecta (The Republic of Maldives)

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Datasets

CCDC 145736: Experimental Crystal Structure Determination

CCDC 145737: Experimental Crystal Structure Determination

Cite this