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。     

具有生理活性的甾体酰胺类化合物

在甾体的甾核或支链上引入不同的官能团后可得到不同生理活性的化合物,它们有可能会成为人类治疗不同疾病的药物,因此甾体药物除了作为传统激素类药物使用外,在抗肿瘤药物、抗炎药物中的应用也成为甾体的重要研究内容之一。含有酰胺官能团的甾体化合物具有很好的生物活性。本文按照酰胺基团在甾体酰胺化合物中的位置进行分类,同时结合本课题组在甾体酰胺化合物的合成和生理活性研究方面所取得的一些成果,概述了近几年来新合成及发现的甾体酰胺类化合物及其衍生物的生理活性及研究进展,包括作为抗肿瘤药物的甾体酰胺化合物的设计、筛选、对5α-还原酶的抑制作用、抑制肿瘤细胞生长增殖活性及抗菌作用,并对此方面的发展趋势、应用前景作了展望。     

Thiophene Scaffold as Prospective Antimicrobial Agent: A Review

Thiophene has emerged as a potent scaffold that has pulled the keen interest of the researchers because of its considerable diversity in biological activities. The versatility of the thiophene nucleus is demonstrated by the successful introduction of its derivatives, which have anti‐inflammatory (Thenaldine), anticancer (Ralitrexed), antioxidant (Erdosteine), and antimicrobial (Cefoxitin and Temocillin) activities. This decent variety in the biological response profile has pulled in the consideration of numerous researchers to research this skeleton to its distinctive potential against several activities. This review is integral to prior reviews and plans to review the work regarding antibacterial and antifungal activities of thiophene, substituted thiophene and thiophene‐like compounds, and also Schiff bases of thiophene and substituted thiophenes from year 1995 to the beginning of 2018.     

Synthesis of Novel Biologically Active s-Triazolo[3,4-b]-1,3,4-thiadiazole Derivatives

Heterocycles bearing a symmetrical triazole or 1,3,4-thiadiazole ring system are reported to show a broad spectrum of biological activities.[1,2] The 1,2,4-triazole nucleus has been recently incorporated into a wide variety of therapeutically interesting drugs including H1/H2 histamine receptor blockers, cholinesterase active agents, CNS stimulants, antianxiety and sedatives[3] Coumarins are nowadays an important group of organic compounds that used as bactericides, fungicides,anti-inflammatory, anticoagulant, anti-HIV and antitumour agents.[4,5] Keeping in view the biological importance of the above mentioned heterocyclic compounds and in continuation of our search for biologically active nitrogen and sulphur heterocycles, a series of s-triazolo[3,4-b]-1,3,4-thiadiazole derivatives was synthesized.     

Thiazole Ring—A Biologically Active Scaffold

Background: Thiazole is a good pharmacophore nucleus due to its various pharmaceutical applications. Its derivatives have a wide range of biological activities such as antioxidant, analgesic, and antimicrobial including antibacterial, antifungal, antimalarial, anticancer, antiallergic, antihypertensive, anti-inflammatory, and antipsychotic. Indeed, the thiazole scaffold is contained in more than 18 FDA-approved drugs as well as in numerous experimental drugs. Objective: To summarize recent literature on the biological activities of thiazole ring-containing compounds Methods: A literature survey regarding the topics from the year 2015 up to now was carried out. Older publications were not included, since they were previously analyzed in available peer reviews. Results: Nearly 124 research articles were found, critically analyzed, and arranged regarding the synthesis and biological activities of thiazoles derivatives in the last 5 years.     

黄酮类化合物结构修饰及抗肿瘤活性研究进展

我国天然药物和中药资源丰富,种类繁多,可作为先导化合物进行修饰以提高可成药性。其中,黄酮类化合物是自然界中一种常见的天然多酚类化合物,在抗肿瘤方面具有其独特的生物活性;对其进行结构修饰与改造,可提高黄酮类化合物的生物利用度和抗肿瘤活性。本文通过查阅并整理近几年国内外的黄酮类化合物的相关文献,对黄酮类化合物的母核位点进行结构修饰与改造所得的101个黄酮类衍生物及其抗肿瘤活性及作用机制进行综述,同时讨论了构效关系,以期为黄酮类衍生物的结构修饰和抗肿瘤研究提供参考和帮助。     

茼蒿素类似物的分子多样性2-(Z)-亚苄基-1,6,9-三氧杂螺环 [4,5-癸-3-烯类化 合物的合成

有多种生物活性的茼蒿素类似物是一类具有螺环缩酮烯醚独特结构的化合物。本文报道用糠醇为原料,以我们的呋喃二醇脱水－螺环缩酮化反应为关键反应,合成了一类三氧杂螺环-[4,5]-癸烯的新型茼蒿素类似物。为这类化合物分子多样性开辟了新的途径。     

Synthesis and Antimicrobial Activity of New Thiazolidine‐Based Heterocycles as Rhodanine Analogues

A new series of compounds containing thiazole nucleus as Rhodanine analogues have been synthesized. The new compounds were prepared from the reactions of the thiosemicarbazones ( 3a,b ) with a series of α‐halo carbonyl compounds to give the corresponding Rhodanine analogues. The thiosemicarbazones derivatives ( 3a,b ) were reacted also with hydrazonoyl chlorides to afford the corresponding tri‐substituted and tetra‐substituted thiazoles. The structures of the newly synthesized compounds were confirmed by elemental analysis and spectral data. The biological activities of the new synthesized Rhodanine analogues' were evaluated for their antimicrobial activities. The results showed that some of these compounds showed excellent activity against two fungal strains, including Aspergillus niger and Aspergillus flavus, in addition to three yeast strains, including Saccharomyces cervesi, Candida albicans NRRL Y‐477, and Candida Pathological specimen compared with the ketoconazol, as the reference drug.     

Overview on the recently developed coumarinyl heterocycles as useful therapeutic agents

The chemical class of benzopyrones consists of a large number of compounds possessing the benzene ring fused with the oxygen containing pyrone ring. This class is further divided into the benzo-γ-pyrone i.e. flavonoids and the benzo-α-pyrone i.e. coumarins. Coumarins, the 2H-chromen-2-one and its related analogues exhibit a multitude of biological activities. Attempts made in the continuous chemical diversification of this parent nucleus have brought significant alterations in the biological activity among the generated compounds and therefore, this category of benzopyrones has been much exploited in the current medicinal chemistry research. Thus, it was thought worthwhile to present a review on the newly synthesised heterocyclic coumarinyl derivatives with their physicochemical parameters and biological activity, attempted by our co-workers. This review also creates a platform for highlighting approaches and strategies used in the chemical synthesis of coumarinyl compounds along with their biological activity relating to their structure.     

含吡唑环的1,2,4-三唑希夫碱类衍生物的合成及生物活性

以自制的4-氨基-4,5-二氢-3-[(3,5-二甲基吡唑-1-基)甲基]-1,2,4-三唑-5-硫酮衍生物为中间体, 与取代苯甲醛反应合成了一系列新型含吡唑环的1,2,4-三唑希夫碱衍生物. 通过红外光谱、 核磁共振波谱、 高分辨质谱、 元素分析及X射线单晶衍射对目标化合物进行了结构表征, 并初步测试了其生物活性. 结果表明, 大部分化合物表现出较好的抑菌活性, 其中化合物G9, G10和G15的抑菌效果优于对照药三唑酮.     

具有生理活性的含氧、氮、硫杂原子螺环化合物的研究进展

综述了近年来部分具有生理活性螺环化合物的研究进展, 重点介绍了这类化合物的结构特征、生理活性和部分化合物的合成方法. 展望了该类螺环化合物的应用前景.     

天然5,7-二羟基-3-异戊烯基黄酮与5-羟基-3-异戊烯基黄酮的全合成

以2,4,6-三羟基苯乙酮和2,6-二羟基苯乙酮为原料, 分别通过甲基保护酚羟基、 苯甲酰氯酰化、 Bake-Venkataraman重排、 异戊烯基化、 酸催化关环及EtSLi脱去甲基等6步反应, 以高收率完成了天然5,7-二羟基-3-异戊烯基黄酮(1a, 收率80.6%)和5-羟基-3-异戊烯基黄酮(1b, 收率84.9%)的全合成, 所有化合物均经 ¹H NMR 和 ¹³C NMR表征确定. 通过密度泛函理论方法对目标产物(1a和1b)的生物活性进行了预测. 结果表明, 3位异戊烯基侧链的存在能大大增强化合物相应的生物活性, 而且是化合物生物活性增强必需的取代基. 另外, 目标产物1a的生物活性高于产物1b, 归因于黄酮类化合物分子中A环上的7-OH属增效基团, 起到增强生物活性的作用, 化合物1a分子中A环上有7-OH, 而化合物1b分子中则无该基团. 本合成方法对其它3-烃基黄酮类天然化合物的合成具有潜在的适用性, 所预测的生物活性结果为3-烃基黄酮类化合物的构效关系研究奠定了基础.     

芳基脲类衍生物的合成、活性和量子化学计算

芳基脲类化合物是抑制细胞分裂生长的一种抑制剂。本研究报导合成的六个芳基脲类化合物,并利用油菜试法测定了它们抑制油菜胚根生长的生物活性;采用MOPAC程序中的PM3方法进行了量化计算,计算结果较好地解释了新合成化合物结构与生物活性的相关性。     

均三唑并噻二唑:重要的潜在药物结构单元

均三唑并噻二唑是一类重要的稠杂环化合物,其衍生物具有抗菌、消炎、抗肿瘤、抗结核、酶抑制作用、调节植物生长等多种生物活性。本文按照均三唑并噻二唑类化合物呈现的不同生物活性进行分类,综述了近年来该类化合物在上述领域的研究进展。     

A Review: Halogenated Compounds from Marine Actinomycetes

Marine actinomycetes, Streptomyces species, produce a variety of halogenated compounds with diverse structures and a range of biological activities owing to their unique metabolic pathways. These halogenated compounds could be classified as polyketides, alkaloids (nitrogen-containing compounds) and terpenoids. Halogenated compounds from marine actinomycetes possess important biological properties such as antibacterial and anticancer activities. This review reports the sources, chemical structures and biological activities of 127 new halogenated compounds originated mainly from Streptomyces reported from 1992 to 2020.     

Influence of dipole moments on the medicinal activities of diverse organic compounds

In this study, synthesis, biological activity and structure-activity relationships of diverse compounds are described. In general, the relationships between dipole moment and biological activities are discussed in detail. Despite progress of interdisciplinary science, the use of dipole moment values of organic compounds to understand their potent medicinal activities in various diseases remains unexplored. In contrast, it can be seen that many compounds demonstrate a direct correlation between biological activity and dipole moment. Therefore, analyzing the dipole moment values, scientists may design more potent compounds prior to their synthesis which is tedious, costly and time-consuming.     

An Update on Synthesis of Coumarin Sulfonamides as Enzyme Inhibitors and Anticancer Agents

Coumarin is an important six-membered aromatic heterocyclic pharmacophore, widely distributed in natural products and synthetic molecules. The versatile and unique features of coumarin nucleus, in combination with privileged sulfonamide moiety, have enhanced the broad spectrum of biological activities. The research and development of coumarin, sulfonamide-based pharmacology, and medicinal chemistry have become active topics, and attracted the attention of medicinal chemists, pharmacists, and synthetic chemists. Coumarin sulfonamide compounds and analogs as clinical drugs have been used to cure various diseases with high therapeutic potency, which have shown their enormous development value. The diversified and wide array of biological activities such as anticancer, antibacterial, anti-fungal, antioxidant and anti-viral, etc. were displayed by diversified coumarin sulfonamides. The present systematic and comprehensive review in the current developments of synthesis and the medicinal chemistry of coumarin sulfonamide-based scaffolds give a whole range of therapeutics, especially in the field of oncology and carbonic anhydrase inhibitors. In the present review, various synthetic approaches, strategies, and methodologies involving effect of catalysts, the change of substrates, and the employment of various synthetic reaction conditions to obtain high yields is cited.     

Total synthesis of naturally occurring chiral cyclopropane fatty acids and related compounds

Cyclopropane fatty acids (CFAs) and related compounds containing CFAs commonly occur in various natural sources, including plants or microorganisms. Some CFAs exhibit intriguing biological activities such as antifungal or immunosuppressive activities. Due to their biological importance and structural features, a number of synthetic studies have been conducted to date. These total syntheses have helped to elucidate their structural determinants or biological activities. Herein the total syntheses of naturally occurring CFAs and related compounds are summarized.     

The Effects of Processing on Bioactive Compounds and Biological Activities of Sorghum Grains

Sorghum is ranked the fifth most commonly used cereal and is rich in many kinds of bioactive compounds. Food processing can affect the accumulation and decomposition of bioactive compounds in sorghum grains, and then change the biological activities of sorghum grains. The present review aims to analyze the effects of processing technologies on bioactive compounds and the biological activities of sorghum grains. Decortication reduces the total phenols, tannins, and antioxidant activity of sorghum grains. The effects of thermal processes on bioactive compounds and potential biological activities of sorghum grains are complicated due to thermal treatment method and thermal treatment conditions, such as extrusion cooking, which has different effects on the bioactive compounds and antioxidant capacity of sorghum due to extrusion conditions, such as temperature and moisture, and food matrices, such as whole grain and bran. Emerging thermal processes, such as microwave heating and high-pressure processing, could promote the release of bound phenolic substances and procyanidins, and are recommended. Biological processes can increase the nutritive and nutraceutical quality and reduce antinutritional compounds, except for soaking which reduces water-soluble compounds in sorghum.     

Zanthoxylum Species: A Comprehensive Review of Traditional Uses,Phytochemistry, Pharmacological and Nutraceutical Applications

Zanthoxylum species (Syn. Fagara species) of the Rutaceae family are widely used in many countries as food and in trado-medicinal practice due to their wide geographical distribution and medicinal properties. Peer reviewed journal articles and ethnobotanical records that reported the traditional knowledge, phytoconstituents, biological activities and toxicological profiles of Z. species with a focus on metabolic and neuronal health were reviewed. It was observed that many of the plant species are used as food ingredients and in treating inflammation, pain, hypertension and brain diseases. Over 500 compounds have been isolated from Z. species, and the biological activities of both the plant extracts and their phytoconstituents, including their mechanisms of action, are discussed. The phytochemicals responsible for the biological activities of some of the species are yet to be identified. Similarly, biological activities of some isolated compounds remain unknown. Taken together, the Z. species extracts and compounds possess promising biological activities and should be further explored as potential sources of new nutraceuticals and drugs.