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Publications (4) View all
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Article: Functional attenuation of human sperm by novel, non-surfactant spermicides: precise targeting of membrane physiology without affecting structure.
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ABSTRACT: We have attempted to identify structural, physiological and other targets on human sperm vulnerable to the spermicidal action of two novel series of non-detergent molecules, reported to irreversibly immobilize human sperm in <30 s, apparently without disrupting plasma membrane. Three sperm samples were studied. Scanning and transmission electron microscopy were used to assess structural aberrations of sperm membrane; plasma membrane potential and intracellular pH measurements (fluorometric) were used to detect changes in sperm physiology; reactive oxygen species (ROS, fluorometric) and superoxide dismutase activity (colorimetric) were indicators of oxidative stress; and sperm dynein ATPase activity demonstrated alterations in motor energy potential, in response to spermicide treatment. Post-ejaculation tyrosine phosphorylation of human sperm proteins (immunoblotting) was a marker for functional integrity. Disulfide esters of carbothioic acid (DSE compounds) caused complete sperm attenuation at > or =0.002% concentration with hyper-polarization of sperm membrane potential (P < 0.001), intracellular alkalinization (P < 0.01), ROS generation (P < 0.05) and no apparent effect on sperm (n = 150) membrane structure. Isoxazolecarbaldehyde compounds required > or =0.03% for spermicidal action and caused disrupted outer acrosomal membrane structure, depolarization of membrane potential (P < 0.001), intracellular acidification (P < 0.01) and ROS generation (P < 0.01). Detergent [nonoxynol-9 (N-9)] action was sustainable at > or =0.05% and involved complete breakdown of structural and physiological membrane integrity with ROS generation (P < 0.001). All spermicides caused functional attenuation of sperm without inhibiting motor energetics. Unlike N-9, DSE-37 (vaginal dose, 200 microg) completely inhibited pregnancy in rats and vaginal epithelium was unchanged (24 h,10 mg). The study reveals a unique mechanism of action for DSE spermicides. DSE-37 holds promise as a safe vaginal contraceptive. CDRI Communication No. 7545.Human Reproduction 02/2010; 25(5):1165-76. · 4.47 Impact Factor -
Article: Simple and efficient synthesis of substituted 2-pyrrolidinones, 2-pyrrolones, and pyrrolidines from enaminones of Baylis-Hillman derivatives of 3-isoxazolecarbaldehydes.
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ABSTRACT: The enaminones, generated from derivatives of appropriately substituted Baylis-Hillman adducts of 3-isoxazolecarbaldehydes, undergo intramolecular ring-closure reactions to afford substituted 2-pyrrolidinones, 1,5-dihydro-2-pyrrolones, and N-substituted pyrrolidines in good yields.The Journal of Organic Chemistry 02/2005; 70(1):353-6. · 4.45 Impact Factor -
Article: TiCl(4)-promoted Baylis-Hillman reactions of substituted 5-isoxazolecarboxaldehydes with cycloalkenones).
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ABSTRACT: The Baylis-Hillman (BH) reaction of substituted 5-isoxazolecarboxaldehydes with cyclohexenone in the presence of TiCl(4) invariably lead to the formation of hemiacetals beside the BH adducts. A similar reaction in the presence of DABCO, DBU, or 3-HQN yielded minor quantities of phenols in addition to the usual BH adducts. Similar to 5-isoxazolecarboxaldehydes, the TiCl(4)-mediated BH reaction of cyclohexenone with various benzaldehydes also furnishes hemiacetals in considerable yields. The reaction mechanism involving the formation of alpha-chloromethyl enone as an intermediate has been proposed. The synthesis of hemiacetals 5 and 14 from compound 4 in the presence of cyclohexenone and cyclopentenone, respectively, under acidic conditions indicates that enolization and aromatization of the cyclohexene ring are the key steps in the reaction mechanism.The Journal of Organic Chemistry 09/2002; 67(16):5783-8. · 4.45 Impact Factor -
Article: TiCl4-Promoted Baylis−Hillman Reactions of Substituted 5-Isoxazolecarboxaldehydes with Cycloalkenones1
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ABSTRACT: The Baylis−Hillman (BH) reaction of substituted 5-isoxazolecarboxaldehydes with cyclohexenone in the presence of TiCl4 invariably lead to the formation of hemiacetals beside the BH adducts. A similar reaction in the presence of DABCO, DBU, or 3-HQN yielded minor quantities of phenols in addition to the usual BH adducts. Similar to 5-isoxazolecarboxaldehydes, the TiCl4-mediated BH reaction of cyclohexenone with various benzaldehydes also furnishes hemiacetals in considerable yields. The reaction mechanism involving the formation of α-chloromethyl enone as an intermediate has been proposed. The synthesis of hemiacetals 5 and 14 from compound 4 in the presence of cyclohexenone and cyclopentenone, respectively, under acidic conditions indicates that enolization and aromatization of the cyclohexene ring are the key steps in the reaction mechanism.07/2002;
