具有特殊甾核结构甾体化合物的合成及生理活性研究进展

改变甾体的甾核结构,在甾核或支链中引入不同的官能团,可以得到一些具有不同生理活性的化合物.按照不同类型甾核结构分类,结合本课题组在具有特殊甾核结构甾体化合物的合成和生理活性研究方面所取得的一些成果,对近年来具有A-失碳甾体化合物、B-失碳甾体化合物及C-失碳-D-增碳甾体化合物的合成及生理活性进行讨论,并展望了此类化合物的发展趋势及应用前景.     

硒氰酸酯合成方法及硒氰酸酯化合物生物活性研究进展

硒元素作为生物体的必需微量元素,在人类的生长及发育过程中发挥着极其重要的生理作用。有机硒化合物在抗氧化、抗炎、抗肿瘤等方面展现出卓越的生物活性,对有机硒化合物的开发应用研究是目前化学、生命科学、临床医学等研究领域的一个研究热点。硒氰酸盐是有机硒中的一类含硒化合物,近年来,很多学者开发了不少在有机化合物中直接引入硒氰基官能团的新方法,并合成了许多新型有机硒氰基化合物,这些化合物显示出不同的生物活性,引起人们对硒氰基官能团的极大兴趣。本文主要综述了硒氰酸酯化合物的合成方法研究及非甾体硒氰基化合物和甾体硒氰基化合物的研究进展,并初步探讨有机硒的发展及应用前景,希望为具有不同生物活性的新型有机硒分子的设计合成提供有用参考。     

芳(杂)环甾体化合物的合成及生理活性研究

芳(杂)环甾体化合物是一类具有显著生理活性的化合物,它们往往具有很好的抗菌、抗炎和抗肿瘤活性。本文根据此类化合物的结构类型进行分类,讨论近年来芳(杂)环甾体化合物的合成及生物活性研究进展,并对其发展趋势和应用前景进行了展望。     

具有生理活性甾体金属配合物的研究进展

按照金属离子与甾体配体之间的连接方式对甾体金属配合物进行分类。综述了近年来合成的甾体金属配合物及其抗肿瘤、抗菌等多种生理活性研究进展,并对此类化合物发展趋势、应用前景作出展望。     

7-位取代的甾体类化合物生物活性研究进展

7-位取代的甾体类化合物是一类具有良好生物活性的化合物,在抗炎、抗肿瘤等领域发挥着重要作用.本文以7-位取代的甾体类化合物为研究对象,按照不同的留体母核进行分类,对近年来有关7-位取代的甾体类化合物的生理活性研究进行综述,并为此类化合物的发展趋势和应用作了展望,以期为抗肿瘤药物的研发提供一定的理论基础.     

具有抗肿瘤活性甾体氮芥类化合物的研究进展

本文按照甾体的甾核结构对甾体氮芥化合物进行分类,综述了近年来新合成的甾体氮芥类化合物及其衍生物的抗肿瘤活性及研究进展,并对此方面的发展趋势和应用前景作了展望。     

3-羟基-6-腙及6-羰基-3-腙胆甾烷的合成及抗肿瘤活性评估

以胆甾醇为原料,通过不同的合成方法,制备得到8个新的具有3-羟基-6-腙及3个6-羰基-3-腙结构的胆甾烷腙衍生物,所有合成化合物都通过了IR,NMR及HRMS的结构表征.另外,采用人肝癌细胞(Bel-7404)及胃癌细胞(SGC-7901)对合成化合物的抗肿瘤活性进行了研究,结果表明所合成的3-羟基-6-腙胆甾烷衍生物对所测试的肿瘤细胞株表现出明显的生长增殖抑制活性,本研究结果为甾体抗肿瘤药物的合成研究提供了有用的参考.     

22-降-豆甾-22-含氮化合物的合成及抗肿瘤活性

通过结构改造,合成了不同支链的甾体化合物并测定了它们的抗肿瘤细胞增殖活性,探讨了不同支链对抗肿瘤活性的影响。     

甾体内酯化合物的合成及生物活性研究进展

某些具有生理活性及结构特殊的甾体内酯类化合物引起了化学家的浓厚兴趣。本文按照不同的结构分类,对近年来有关甾体内酯化合物及其衍生物的合成和生理活性研究中具有代表性的工作进行综述,并对此方面的发展趋势、应用前景进行展望。     

核外氮杂甾体的合成及其抗肿瘤活性研究进展

合成氮杂甾体并评估其生物学活性是甾体化学和甾体新药研发领域的热点之一.通过总结近期发表的相关文献,重点介绍核外氮杂甾体如甾体螺吲哚酮类化合物、三氮唑连接的甾体杂合体及天然氮杂甾体的合成及其抗肿瘤活性的最新进展.     

Diastereoselective aminocarbonylation of a steroidal iodoalkene with 2,2′-diamino-1,1′-binaphthalene in palladium-catalysed reactions

A palladium-catalysed aminocarbonylation of a steroidal iodoalkene (17-iodo-5α-androst-16-ene) model compound with 2,2′-diamino-1,1′-binaphthalene as an N-nucleophile was carried out. The combination of a steroidal skeleton possessing central elements of chirality and a binaphthyl moiety with axial chirality was carried out resulting in a novel type of steroidal carboxamides. The binaphthalene—steroid conjugates are potential 5α-reductase inhibitors. Both epimers of the monocarboxamide and those of the dicarboxamide, formed with moderate diastereoselectivity, were isolated and fully characterised.     

Novel 4-azaandrostenes as prostate cancer cell growth inhibitors: Synthesis,antiproliferative effects,and molecular docking studies

In this study, synthesis, structural characterization, molecular docking studies, and antiproliferative effects in four different cell lines of several novel 16-arylidene-4-azaandrost-5-ene compounds are reported. These compounds were prepared by oxidative cleavage of the enone system of androstenedione followed by an azacyclization reaction and an aldol condensation with various aldehydes at C16. In the androgen-dependent LNCaP cells, the most relevant antiproliferative effects were observed with the 16-phenyl, 16-p-tolyl, and 16-p-nitrophenyl derivatives. Compound 16E-[(4-methylphenyl)methylidene]-4-azaandrost-5-ene-3,17-dione was the most potent in these cells (IC₅₀ = 28.28 μM), having lower antiproliferative effects in the androgen-independent PC-3 cells (IC₅₀ = 45.31 μM). In addition, an interesting selectivity toward cancer cell lines was found for all compounds because a generally low cytotoxicity was detected in healthy human fibroblasts. Furthermore, the 16-p-tolylazaandrostene steroid induced a reduction of viability in LNCaP cells similar to that observed with finasteride, a clinically used 5α-reductase inhibitor. Moreover, molecular docking studies predicted that these 4-azaandrostene derivatives can interact with 5β-reductase, which has a high level of similarity to 5α-reductase enzyme, and with other common targets of steroidal drugs, particularly the enzyme 17α-hydroxylase/17,20-lyase.     

Synthesis and 5α-reductase inhibitory activity of C₂₁ steroids having 1,4-diene or 4,6-diene 20-ones and 4-azasteroid 20-oximes

The synthesis and evaluation of 5α-reductase inhibitory activity of some 4-azasteroid-20-ones and 20-oximes and 3β-hydroxy-, 3β-acetoxy-, or epoxy-substituted C?? steroidal 20-ones and 20-oximes having double bonds in the A and/or B ring are described. Inhibitory activity of synthesized compounds was assessed using 5α-reductase enzyme and [1,2,6,7-3H]testosterone as substrate. All synthesized compounds were less active than finasteride (IC??: 1.2 nM). Three 4-azasteroid-2-oximes (compounds 4, 6 and 8) showed good inhibitory activity (IC??: 26, 10 and 11 nM) and were more active than corresponding 4-azasteroid 20-ones (compounds 3, 5 and 7). 3β-Hydroxy-, 3β-acetoxy- and 1α,2α-, 5α,6α- or 6α,7α-epoxysteroid-20-one and -20-oxime derivatives having double bonds in the A and/or B ring showed no inhibition of 5α-reductase enzyme.     

Intramolecular interchain reactions in bidesmosidic glycosides, a new insight into carbohydrate rearrangements induced by electrospray ionisation

Glycoconjugates are a class of complex molecules that are widely distributed in the plant kingdom and in some marine organisms. This class of compounds has a wide range of biological activities such as anti-inflammatory, antimicrobial, antifungal, anticancer, antiulcer, and immunoenhancing actions.1-3 Some of them also show various toxic activities such as cytotoxic, hemolytic, cardiotoxic, and teratogenic. Among these compounds, steroidal and triterpenoid saponins have long been known as components of widely used herbal drugs and pharmaceutical preparations; ginseng, Tribulus terrestris, Quillaja saponaria, and Digitalis ssp. are just a few examples. Thus, identification of saponins in herbal drugs used worldwide is of significance in phytochemical and toxicological quality control studies, and for the production of safe health products. Therefore, there is continuing demand for methods to rapidly identify and characterize these natural products.     

On the formation of homo-aza-steroids and derivatives by beckmann rearrangement. Antitumor activity of stereoisomers homo-aza-steroidal esters

The Beckmann rearrangement of steroidal oximes is reported. Different methods of esterification of homo-aza-steroids with carboxylic derivatives of N,N-bis(2-chloroethyl)aniline are reported. The lipophilic nature of the steroidal hormones is the reason for searching compounds containing as the biological platform the steroid molecule and as the active moiety the alkylating agent, such as nitrogen mustards linked to the steroid with a stable bond or with an easily cleaved ester or ether molecule and different other active species, hopefully to transport and deliver the alkylating agent to the specific target tissue. The concept to design hybrid compounds containing as the biological platform steroidal lactams and as the alkylating congener carboxylic derivatives of N,N-bis(2-chloroethyl)aniline might form compounds with synergistic activity. The findings suggest that the conformation of the alkylating agent influences the anticancer activity, while the amide group of the lactam molecule is important for activity in L1210 leukemia. These hybrid compounds with a modified steroid as the biological platform furnish derivatives with advantages compared to the unmodified steroids with alkylating agents. Different methods of esterification of homo-aza-steroids with carboxylic derivatives of N,N-bis(2-chloro-ethyl)aniline are reported.     

3-羰基-4-氮杂-Δ5-雄甾烯-17-肟衍生物的合成及其抑制 5α-还原酶活性研究

以雄甾-4-烯-3,17-二酮(AD)为起始原料, 合成了14个甾体17位肟醚和肟酯类新化合物. 所合成的化合物结构均经过MS, 1H NMR谱确证, 并对所合成的化合物进行了老鼠5α-还原酶抑制生物活性初步评价. 结果表明: 受试化合物均有一定的5α-还原酶抑制活性, 其中化合物5a, 5c, 5d有较高的5α-还原酶抑制活性, 与参比药物Espristeride相当.     

Synthesis and characterization of new phenyl esters derived from 16-dehydropregnenolone acetate (16-DPA)

A series of new phenyl esters based on a 5,16-pregnadiene-20-one skeleton, namely 3β-benzoyloxy-5,16-pregnadiene-20-ones, which may be good inhibitors of 17α-hydroxylase and 5α-reductase enzyme or useful intermediates for producing steroidal drugs, were synthesized starting from diosgenin. The structures of the steroids were characterized by ¹H nuclear magnetic resonance (NMR), ¹³C NMR, infrared (IR), and mass spectra.     

Highlights on Steroidal Arylidene Derivatives as a Source of Pharmacologically Active Compounds: A Review

Steroids constitute a unique class of chemical compounds, playing an important role in physiopathological processes, and have high pharmacological interest. Additionally, steroids have been associated with a relatively low toxicity and high bioavailability. Nowadays, multiple steroidal derivatives are clinically available for the treatment of numerous diseases. Moreover, different structural modifications on their skeleton have been explored, aiming to develop compounds with new and improved pharmacological properties. Thus, steroidal arylidene derivatives emerged as a relevant example of these modifications. This family of compounds has been mainly described as 17β-hydroxysteroid dehydrogenase type 1 and aromatase inhibitors, as well as neuroprotective and anticancer agents. Besides, due to their straightforward preparation and intrinsic chemical reactivity, steroidal arylidene derivatives are important synthetic intermediates for the preparation of other compounds, particularly bearing heterocyclic systems. In fact, starting from arylidenesteroids, it was possible to develop bioactive steroidal pyrazolines, pyrazoles, pyrimidines, pyridines, spiro-pyrrolidines, amongst others. Most of these products have also been studied as anti-inflammatory and anticancer agents, as well as 5α-reductase and aromatase inhibitors. This work aims to provide a comprehensive overview of steroidal arylidene derivatives described in the literature, highlighting their bioactivities and importance as synthetic intermediates for other pharmacologically active compounds.     

Steroidal nitrone inhibitors of 5α-reductase

This paper describes the rational design and synthesis of novel inhibitors of human steroid 5α-reductase. Steroidal nitrones were synthesised via an eight-step sequence from epiandrosterone and were tested for activity against type I and II 5α-reductase isozymes. Judicious placement of the nitrone into the steroid A-ring provided an effective and stable transition-state mimic of the postulated enolate intermediate involved in the conversion of testosterone into dihydrotestosterone.