Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using 1 alpha,2 alpha-oxido-cholesta-5,7-diene-3 beta,25-diol (2) as a starting material, the provitamins of calcitriol with an additional 2 beta-chloro-, 2 beta-fluoro-, and 2 beta-methoxy-substituent (3,4,5) are obtained by transdiaxial opening of the oxirane ring with nucleophiles. An efficient irradiation process is described and used for the synthesis of the 2 beta-substituted calcitriols NS2 (2 beta-Cl), NS6 (2 beta-F), and NS7 (2 beta-OCH3). The affinity of these three vitamin D3 derivatives to the vitamin D receptor (VDR) and was determined. These three A-ring derivatives of 1,25(OH)2D3 were further tested for their proliferation-inhibitory and anti-adipogenic activity and gene regulatoric activity in the vitamin D3-sensitive, murine, mesenchymal cell line C3H10T1/2. The VDR-affinity of the 2 beta-chloro derivative, NS2 (2 beta-Cl), was identical to 1,25(OH)2D3 and its vitamin D binding protein (DBP)-affinity was in the range of 1,25(OH)2D3. NS2 inhibited the proliferation of C3H10T1/2(BMP-4)-cells in the presence of fetal calf serum (FCS) 9 times, and, in the absence of FCS, 111 times lower, as compared with 1,25(OH)2D3. The ID50 dose of adipogenesis-inhibition of NS2 was 13 times higher than the ID50 dose of 1,25(OH)2D3. NS6 (2 beta-F) displayed a slightly higher affinity than 1,25(OH)2D3 to the VDR and DBP-affinity. The proliferation-inhibitory activity in the presence of FCS was 90 times higher, as compared with 1,25(OH)2D3. In the FCS-free proliferation assay NS6 displayed an inhibitory activity in the range of 1,25(OH)2D3. NS6 showed an 5 times higher potency to inhibit (pre)adipocyte-differentiation in C3H10T1/2(BMP-4)-cells than 1,25(OH)2D3. NS7 (2 beta-OCH3) showed the lowest VDR-affinity and the highest DBP-affinity of the tested substances, as compared with 1,25(OH)2D3 (11 times lower and 35 times higher respectively). Its proliferation-inhibitory activity in the FCS-free medium was 9 times and in the FCS-containing assay 67 times lower in comparison with 1,25(OH)2D3. A 1250 times higher NS7-dose was needed to reach the anti-adipogenic potency of 1,25(OH)2D3. All tested substances displayed a similar ability to activate a vitamin D responsive element-regulated reporter gene compared to 1,25(OH)2D3 (NS2 and NS6: 1.3 times higher activity; NS7: 1,4 times lower activity).
Steroids 1998 Dec
PMID:Synthesis and biological activities of 2 beta-chloro-, 2 beta-fluoro-, and 2 beta-methoxy-1 alpha,25-dihydroxyvitamin D3. 987 Feb 60

Dengue virus NS2/NS3 protease because of its ability to cleave viral proteins is considered as an attractive target to screen antiviral agents. Medicinal plants contain a variety of phytochemicals that can be used as drug against different diseases and infections. Therefore, this study was designed to uncover possible phytochemical of different classes (Aromatic, Carbohydrates, Lignin, Saponins, Steroids, Tannins, Terpenoids, Xanthones) that could be used as inhibitors against the NS2B/NS3 protease of DENV. With the help of molecular docking, Garcinia phytochemicals found to be bound deeply inside the active site of DENV NS2B/NS3 protease among all tested phytochemicals and had interactions with catalytic triad (His51, Asp75, Ser135). Thus, it can be concluded from the study that these Gracinia phytochemicals could serve as important inhibitors to inhibit the viral replication inside the host cell. Further in-vitro investigations require confirming their efficacy.
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PMID:Computer Aided Screening of Phytochemicals from Garcinia against the Dengue NS2B/NS3 Protease. 2474 49