Antifertility, spermicidal and ultrastructural effects of gossypol and derivatives administered orally and by intratesticular injections

Hoffer, Anita P.; Agarwal, Ashok; Meltzer, Peter C.; Naqvi, Rehan H.; Matlin, S. A.

doi:10.1016/0010-7824(88)90032-7

Cited by 19 publications

(7 citation statements)

References 16 publications

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“…When using epididymal sperm for in vitro cultures, seminal vesicle and prostate fluids are excluded, leading to discrepancies in results. It is very difficult to compare sperm cell morphological changes during long-term in vivo experiments with brief in vitro studies in that the extent of cellular necrosis can be related to the incubation times of drug media (Waller et al, 1980;Hoffer et al, 1988). In addition, the amount of drug necessary to produce an effect in vitro may be a great deal less than that necessary to cause a similar effect in exposed cells or tissue in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Spermatozoa, spermatids, and spermatocytes of mid-and late stages were identified as gossypol target cells by some investigators (Coutinho et al, 1985;Frick and Danner, 1985;Kalla et al, 1985a;Liu et al, 1985;Ahluwalia et al, 1986;Fei and Teng, 1988;Hoffer et al, 1988;Teng and Fei, 1988;Ueno et al, 1988). These cells were the most susceptible to damage by gossypol, the first to show detectable change, and the first to degenerate.…”

Section: Spermicidal Effects Of Gossypolmentioning

confidence: 99%

“…Gossypol has been reported to exert spermicidal activity upon spermatozoa in vitro (Poso, 1980;Cameron et al, 1982;Wichmann et al, 1983) and in vivo (Kennedy et al, 1982;Tso et al, 1985;Coutinho and Melo, 1988). Spermatozoa, spermatids, and spermatocytes of mid-and late stages were identified as gossypol target cells by some investigators (Coutinho et al, 1985;Frick and Danner, 1985;Kalla et al, 1985a;Liu et al, 1985;Ahluwalia et al, 1986;Fei and Teng, 1988;Hoffer et al, 1988;Teng and Fei, 1988;Ueno et al, 1988). These cells were the most susceptible to damage by gossypol, the first to show detectable change, and the first to degenerate.…”

Section: Spermicidal Effects Of Gossypolmentioning

confidence: 99%

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Effects of gossypol on the motility of mammalian sperm

Porat

1990

Molecular Reproduction Devel

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Section: Discussionmentioning

confidence: 99%

Section: Spermicidal Effects Of Gossypolmentioning

confidence: 99%

Section: Spermicidal Effects Of Gossypolmentioning

confidence: 99%

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Effects of gossypol on the motility of mammalian sperm

Porat

1990

Molecular Reproduction Devel

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“…1 As a natural product, the compound exhibits a wide spectrum of activity, including contraceptive, 2,3 antitumor, [4][5][6][7][8][9] antiamebic, 10 and antiviral effects. 11 Gossypol can also be toxic to animals overfed cottonseed products.…”

mentioning

confidence: 99%

Preparation of enantiomeric gossypol by crystallization

Dowd

2003

Chirality

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Large enantiomorphic crystals of gossypol-acetone (1:3) were grown from acetone solutions of rac-gossypol-acetic acid (1:1) at 4 degrees C. By controlling the initial gossypol concentration, crystallization time, and solution volume, single crystals were grown that weighed >50 mg, equivalent to >37 mg of enantiomeric gossypol. Even larger crystals were possible, but it was difficult to produce these reliably without contamination of the antipode. Essentially all of the acetone within the crystal form was removed by storing the crystals under vacuum for 3-4 days. By employing these techniques, gram quantities of enantiomeric gossypol were prepared in high chemical and optical purity. Based on measured and reported optical rotations, the optical purity of samples prepared by crystallization was greater than the optical purity of samples prepared by chromatographic separation of gossypol-amine diastereomers. The principal limitation of crystallization as a preparative method is the need to determine the chirality and purity of each product crystal. Nevertheless, the method competes favorably with preparative-scale chromatographic procedures.

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“…11,12 In all these cases, the (−)-enantiomer of gossypol has been shown to be substantially more active than the (+)-isomer. [13][14][15][16][17][18][19][20][21] Interest in studies of the varied biological activities of the enantiomers of gossypol [13][14][15][16][17][18][19][20][21] and of its unequal enantiomeric distribution in different Malvaceae species [2][3][4][5] has resulted in a need for simple and rapid methods for the analysis of the enantiomeric composition of gossypol samples, as well as for large-scale methods for the resolution of the racemic compound. Previous efforts to resolve gossypol enantiomers directly by HPLC on chiral stationary phases have been unsuccessful, and as a result it was necessary to develop indirect methods, in which gossypol was converted into Schiff's base derivatives that could be separated on either chiral or achiral phases.…”

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First direct resolution of gossypol enantiomers on a chiral high‐performance liquid chromatography phase

Cass¹,

Bassi²,

Matlin³

1999

Chirality

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The first direct resolution of gossypol enantiomers has been achieved by HPLC on a chiral stationary phase consisting of cellulose tris-(3,5-dimethylphenyl carbamate) coated onto microporous aminopropyl-silica eluted in the reverse phase mode. Chirality 11: 46-49, 1999. © 1999 KEY WORDS: enantiomers of gossypol; direct resolution; chiral HPLC phase; carbohydrate carbamate coating; cellulose tris-(3,5-dimethylphenyl carbamate)Gossypol (Fig. 1), a binaphthyl pigment isolated from the cotton plant and also present in a number of other members of the Malvaceae, is chiral due to steric hindrance to rotation about the internaphthyl bond.1 The standard isolation procedure developed for the extraction of gossypol from the cotton plant 1 affords racemic gossypol as a 1:1 complex with acetic acid. However, investigations have shown that there are wide variations in the ratio of gossypol enantiomers present in different species of cotton plant (Gossypium species) and even within different tissues in the same plant. 2-5There has been considerable interest in the pharmacological properties of gossypol and it has been shown to be potent as an anti-spermatogenic agent 1,6,7 and anti-tumor agent, 8,9 and to possess activity against the HIV-1 virus 10 and the Entamoeba histolytica organism responsible for amoebiasis. 11,12 In all these cases, the (−)-enantiomer of gossypol has been shown to be substantially more active than the (+)-isomer. [13][14][15][16][17][18][19][20][21] Interest in studies of the varied biological activities of the enantiomers of gossypol [13][14][15][16][17][18][19][20][21] and of its unequal enantiomeric distribution in different Malvaceae species [2][3][4][5] has resulted in a need for simple and rapid methods for the analysis of the enantiomeric composition of gossypol samples, as well as for large-scale methods for the resolution of the racemic compound. Previous efforts to resolve gossypol enantiomers directly by HPLC on chiral stationary phases have been unsuccessful, and as a result it was necessary to develop indirect methods, in which gossypol was converted into Schiff's base derivatives that could be separated on either chiral or achiral phases. [22][23][24][25] For the first time, we have now identified conditions suitable for the direct resolution of gossypol enantiomers, using a chiral carbohydrate carbamate phase under reverse phase conditions. MATERIAL AND METHODS ChemicalsAminopropyl-silica (Hypersil-APS, Shandon, UK) had the following properties: particle size, 5 µm; pore size, 120 Å.Isocyanates were purchased from Aldrich (Milwaukee, WI). Solvents were either HPLC grade from Carlo Erba (Milan, Italy) or were purified as usual. 26 Cellulose used was Avicel from Merck. HPLC dead times (t 0 ) were estimated using acetonitrile. (±)-Gossypol acetic acid was isolated from cotton seeds and its separated (−) and (+) enantiomers obtained as described previously. 22-24 EquipmentThe HPLC system consisted of a Shimadzu LC-10AD pump (Kyoto, Japan), a Rheodyne 7125 injector fitted with a 20-µl ...

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Antifertility, spermicidal and ultrastructural effects of gossypol and derivatives administered orally and by intratesticular injections

Cited by 19 publications

References 16 publications

Effects of gossypol on the motility of mammalian sperm

Effects of gossypol on the motility of mammalian sperm

Preparation of enantiomeric gossypol by crystallization

First direct resolution of gossypol enantiomers on a chiral high‐performance liquid chromatography phase

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