1,3,4-oxadiazole: a biologically active scaffold

There has been considerable interest in the development of novel compounds with anticonvulsant, antidepressant, analgesic, anti-inflammatory, antiallergic, antipsychotic, antimicrobial, antimycobecterial, antitumour, antiviral and antitubercular activities. 1,3,4-oxadiazoles constitute an important class of compounds for new drug development. Therefore, many researchers have synthesized these compounds as target structures and evaluated their biological activities. These observations led to the development of new 1,3,4-oxadiazole derivatives. This review article describes the various biological activities associated with 1,3,4-oxadiazole ring system and is useful in guiding the researchers across the world working on this moiety and consequently have been instrumental in the advancement of 1,3,4-oxadiazole chemistry.     

海绵的生物活性研究新进展

海洋物种是生物多样性的来源,能够产生结构多样、生物活性多样的次生代谢物。海绵是其中最丰富的天然产物来源,其药理活性丰富,具有极高的临床应用价值,被认为是药物宝库。目前人们已经发现其具有抗肿瘤、抗病毒、抗菌、抗氧化、抗炎、免疫调节等生物活性。多年来,对海绵的化学成分研究较多,但对其丰富的生物活性研究相对较少。对海绵次生代谢物的生物活性研究现状进行综述,以期发现活性较好的化合物,为新药开发提供依据。此外,还从药物开发领域对进入临床实验的海绵衍生化合物成药性、成本效益等进行讨论。     

Recent researches in triazole compounds as medicinal drugs

Triazole compounds containing three nitrogen atoms in the five-membered aromatic azole ring are readily able to bind with a variety of enzymes and receptors in biological system via diverse non-covalent interactions, and thus display versatile biological activities. The related researches in triazole-based derivatives as medicinal drugs have been an extremely active topic, and numerous excellent achievements have been acquired. Noticeably, a large number of triazole compounds as clinical drugs or candidates have been frequently employed for the treatment of various types of diseases, which have shown their large development value and wide potential as medicinal agents. This work systematically reviewed the recent researches and developments of the whole range of triazole compounds as medicinal drugs, including antifungal, anticancer, antibacterial, antitubercular, antiviral, anti-inflammatory and analgesic, anticonvulsant, antiparasitic, antidiabetic, anti-obesitic, antihistaminic, anti-neuropathic, antihypertensive as well as other biological activities. The perspectives of the foreseeable future in the research and development of triazole-based compounds as medicinal drugs are also presented. It is hoped that this review will serve as a stimulant for new thoughts in the quest for rational designs of more active and less toxic triazole medicinal drugs.     

查尔酮类化合物生物活性研究进展

查尔酮类化合物以1,3-二苯基丙烯酮为基本骨架结构,为多种药用植物的有效成分,具有广泛的生物学活性,因此人们对此类化合物进行了大量研究。了解该类化合物的药理作用机制和构效关系,可为新药设计和开发提供先导化合物或药物资源。现对查尔酮类化合物的抗肿瘤、抗寄生虫、抗HIV、抗炎等多种生物学活性的药理作用机制及构效关系进行了综述。     

The biological potentials of substituted 1,2-diazines: a review on versatile pyridazine derivatives

Many studies have been performed on the pyridazine (1,2-diazine) derivatives in the past decade. This heterocyclic nucleus possesses almost all types of pharmacological activities. This small and simple pyridazine nucleus is present in various compounds that are involved in the research aiming to evaluate new compounds with interesting biological activities, including anti-bacterial, anti-fungal, anti-viral, analgesic, anti-inflammatory, anti-platelets, anti-ulcer, anti-secretory, anti-depressants, anxiolytics, sedative-hypnotics, anti-convulsant, anti-tumor, anti-thrombotics, cardiotonics, vasodilatators, anti-arrhythmics, anti-diabetic, anti-tubercular agents and so on. This review focuses on the pyridazine derivatives with potential activities that have been developed. Pyridazine compounds draw attention of scientists and researchers because of their diverse biological activities as well as simple chemical and easy functionalization at various ring positions, making them attractive synthetic building blocks for designing and development of novel pyridazinone-based therapeutic agents.     

环烯醚萜类化合物的结构和生物学活性研究进展

目的：详细综述了新发现的、具有较新结构特点的环烯醚萜类化合物及生物学活性研究,为环烯醚萜类化合物的结构活性研究提供新的思路。方法：查阅总结近30年国内外发表的关于环烯醚萜新化合物的文献,总结结构和活性的研究概况。结果：环烯醚萜的主要结构类型环烯醚萜苷类、裂环环烯醚萜和环烯醚萜酯。环烯醚萜类化合物主要临床生物活性具有神经系统的保护作用、抗肿瘤作用和保肝作用等。结论：环烯醚萜类化合物的分布广泛,具有较大的药用价值。通过对环烯醚萜类化合物结构和生物学活性的总结和分析,探讨环烯醚萜化合物结构与活性之间的关系,为药物开发和利用提供文献和数据支持。     

The effect of pyridazine compounds on the cardiovascular system

Many natural as well as synthetic heterocylic compounds are known to have different biological activities. The pyridazine moiety is an important structural feature of many biologically active compounds and show diverse pharmacological properties. Pyridazines hold considerable interest relative to the preparation of organic intermediates and physiologically active compounds. However, some compounds bearing pyridazinone rings have been reported to be effective in different cardiovascular diseases. On the basis of the reported literature, we study here on pyridazine compounds to their different biological activities on cardiovascular system. Pyridazinones further draw our focused attention because of their easy fictionalization at various ring positions, which makes them attractive synthetic compounds for designing and development of novel pyridazinone as cardiotonic agents in future.     

Marine-derived drugs in neurology

The oceans provide a rich source of structurally unique compounds that have demonstrated significant biological activities in a range of indications. In particular, the development of marine compounds is emerging as an important field for neurology. Several marine-derived compounds are currently in clinical trials or have been launched for the treatment of neuropathic pain, schizophrenia and Alzheimer's disease. This review describes the development of several of these compounds, specifically covering the conopeptides, anabaseine and omega-3 fatty acids for the potential treatment of various neurological disorders.     

Styryl lactones and their derivatives: biological activities, mechanisms of action and potential leads for drug design

Nature is an inexhaustible source of natural compounds with interesting biological activities. In general, natural products are an important source of new compounds with a variety of structural arrangements and singular properties. Styryl lactones are a group of secondary metabolites ubiquitous in the genus Goniothalamus that have demonstrated to possess interesting biological properties, in particular antiproliferative activity against cancer cells. In general, the cytotoxicity of styryl lactones appears to be specific against cancer cells since insignificant effects of these compounds on normal cells are reported. A large body of evidence suggests that the antiproliferative activity of styryl lactones is associated with the induction of apoptosis in target cells. In the first part of this review we discuss the biological activities of styryl lactones focusing on cancer cells, the causal agent of Chagas' disease and the vectors for yellow fever and human lymphatic filariasis. Stru described in detail for ninety styryl lactones. The last part describes the molecular targets of styryl lactones for inducing apoptosis, as well as immunosuppressive and inflammatory processes. Overall, understanding how these compounds exert their activities in biological system is essential for future development and application of styryl lactones for human health.     

Simple coumarins and analogues in medicinal chemistry: occurrence, synthesis and biological activity

Coumarins, also known as benzopyrones, are present in remarkable amounts in plants, although their presence has also been detected in microorganisms and animal sources. The structural diversity found in this family of compounds led to the division into different categories, from simple coumarins to many other kinds of policyclic coumarins, such as furocoumarins and pyranocoumarins. Simple coumarins and analogues are a large class of compounds that have attracted their interest for a long time due to their biological activities: they have shown to be useful as antitumoural, anti-HIV agents and as CNS-active compounds. Furthermore, they have been reported to have multiple biological activities (anticoagulant, anti-inflammatory), although all these properties have not been evaluated systematically. In addition, their enzyme inhibition properties, antimicrobial and antioxidant activities are other foremost topics of this field of research. The present work is to survey the information published or abstracted from 1990 till 2003, which is mainly related to the occurrence, synthesis and biological importance of simple coumarins and some analogues, such as biscoumarins and triscoumarins. Data are also highlighted, concerning the development of new synthetic strategies that could help in drug design and in the work on SAR or QSAR.     

Progress in the development of peroxide-based anti-parasitic agents

Although unmatchable in their fast clinical response, first generation artemisinin analogs have short biological half-lives, a drawback that results in recrudescence. Efforts during the past decade have identified a number of new artemisinin derivatives with superior therapeutic profiles. As parasitic infections are more prevalent in underdeveloped nations, cost effectiveness during large-scale production of drug candidates remains as the key factor that can affect their success. Apart from compounds that retain an artemisinin core, information pertaining to the mode of action of this natural product has been helpful in the development of new synthetic peroxides with promising biological activities. A commendable success in this area is the compound OZ277 (or RBx-11160)—an orally active synthetic ozonide. A combination of this drug with piperaquine has been selected for phase III clinical trials. Related studies have shown that parasites belonging to genera such as leishmania, schistosoma, trypanosoma and toxoplasma are also susceptible to the artemisinin class of compounds, showing their potential as broad-spectrum anti-infective agents. In addition to artemisinin, a large number of peroxide-containing natural products with interesting biological properties have been isolated from plant and marine sources. Structure-optimization and structure–activity relationship studies involving these new skeletons hold lot of promise in the area of peroxide-based anti-infective agents.     

Acanthella属海绵化学成分及生物活性的研究进展

目的对Acanthella属海绵的化学成分及其生物活性进行综述。方法通过综述国内外相关文献,归纳总结了该属海绵的研究概况。结果从该属海绵中已分离鉴定110个化合物,主要为含有异腈基、异硫氰酸酯和甲酰胺等含氮基团的倍半萜、二萜类化合物。这类化合物具有抗疟、抗虫、抗污损、抗肿瘤、抗菌等多样的生物活性。结论为Acanthella属海绵的化学成分及生物活性的进一步研究提供依据。     

3,6-二取代-5,6-二氢-1,2,4-均三唑并［3,4-b］-1,3,4-噻二唑的合成及抗菌活性

1 ,2 ,4 三唑类杂环化合物有广泛的生物活性 ,如抗菌、抗痉挛、消炎、抗血小板凝聚及调节植物生长等[1- 3 ] 。噻二唑类杂环衍生物也有广泛的生物活性 ,如消炎、驱虫、除草、调节植物生长、防止水稻白叶枯病、柑桔溃疡病和蕃茄青枯病等[4 - 6] 。对噻二唑衍生物的合成前文[7] 曾做过报道。在此基础上 ,本文用 3 对硝基苯氧甲基 4 氨基 5 巯基 1,2 ,4 三唑和醛合成了 9个新化合物 (2ａ - 2ｉ) (图 1)。Ｓｃｈｅｍｅ 1　Ｒｏｕｔｅｏｆｓｙｎｔｈｅｓｉｓｏｆｃｏｍｐｏｕｎｄｓ 2ａ - 2ｉＴａｂ 1　Ｐｈｙｓｉｃａｌｃｏｎｓｔａｎｔｓ…     

Marine peptides and related compounds in clinical trial

Advances in the sophisticated instruments for the isolation and characterization of marine natural products, and development in the biological assay systems, have resulted in the discovery of various compounds of biomedical application. Marine natural products have been a source of new leads for the treatment of many deadly diseases such as cancer, acquired immuno-deficiency syndrome (AIDS) etc. The compounds of marine origin are diverse in structural class from simple linear peptides to complex macrocyclic polyethers. Number of marine peptides have been isolated in recent years which exhibit potent biological activities, and many of the compounds showed promising anticancer activity. Didemnin was the first marine peptide that entered in human clinical trials in US for the treatment of cancer, and other anticancer peptides such as kahalalide F, hemiasterlin, dolastatins, cemadotin, soblidotin, didemnins and aplidine have entered in the clinical trials. Clinical status of anticancer marine derived peptides have been discussed and reviewed.     

Natural peroxy anticancer agents

Present review describes research on novel natural anticancer agents isolated from terrestrial and marine sources. More than 120 cytotoxic anticancer compounds have shown confirmed activity in vitro tumor cell lines bioassay and are of current interest to Natural Cancer Institute for further in vivo evaluation. Intensive searches for new classes of pharmacologically potent agents produced by terrestrial and marine organisms have resulted in the discovery of dozens of compounds possessing high cytotoxic activities. However, only a limited number of them have been tested in pre-clinical and clinical trials. One of the reasons is a limited supply of the active ingredients from the natural sources. However, the pre-clinical and clinical development of many terrestrial and/or marine-derived natural products into pharmaceuticals is often hampered by a limited supply from the natural source. Total synthesis is of vital importance in these situations, allowing for the production of useful quantities of the target compound for further biological evaluation. With computer program PASS some additional biological activities are also predicted, which point toward new possible applications of these compounds. This review emphasizes the role of terrestrial and marine peroxides as an important source of leads for drug discovery.     

海洋来源的放线菌次级代谢产物及其生物活性

放线菌是迄今最重要和最大的药用微生物种群。海洋放线茵生存于苛刻特殊的海洋环境，使其具备了复杂独特的代谢途径，其次级代谢产物在结构类型以及在生物活性等方面都呈现出与陆生放线茵不同的特点和多样性。多年来，诸多结构新颖、生物活性显著的天然活性产物持续从海洋来源放线茵代谢产物中被发现，这些活性化合物为新药研究提供了丰富的先导化合物，有些已进入研发阶段。近年，海洋放线茵活性产物的研究仍然是海洋微生物产物研究中值得关注的一个热点。本文按化舍物结构类型简要介绍了海洋来源放线茵代谢产物及其生物活性的研究概况。     

磺胺噻二嗪硫酮衍生物的合成及其抑菌活性

利用药物化学骈合原理设计并合成了一系列新的３，５－二取代１，３，５－噻二嗪－２－硫酮类化合物，其结构经红外光谱，紫外光谱及元素分析证实，抑菌活性试验显示了良好的抑菌活性。     

Specific bradycardic agents. 2. Heteroaromatic modifications in the side chain of specific bradycardic benzazepinones: chemistry, pharmacology, and structure-activity relationships

Compound 1 (UL-FS 49) has recently been described as the representative of a novel class of antiischemic compounds termed "specific bradycardic agents". In search of specific bradycardic agents with different pharmacokinetic profiles, heteroaromatic analogues of 1 have been synthesized and evaluated for their bradycardic activity, selectivity, and duration of action. The chain length n and the nature of the heteroaromatic system of compounds 2 strongly determine the biological activities. Unsubstituted benzothiophenes and benzofurans in combination with a chain length of n = 2 give the most active bradycardic compounds. Some of the new compounds combine high bradycardic potency and selectivity with a short duration of action and may thus be useful for the development of short-acting specific bradycardic drugs.     

Recent advances on structural modifications of benzothiazoles and their conjugate systems as potential chemotherapeutics

INTRODUCTION: Benzothiazole scaffold comprises a bicyclic ring system and is known to exhibit a wide range of biological properties including antimicrobial and anticancer activities. Benzothiazole derivatives have long been therapeutically used for the treatment of various diseases. However, in recent years, 2-arylbenzothiazoles have emerged as an important pharmacophore in the development of antitumor agents. The promising biological profile and synthetic accessibility have been attractive in the design and development of new benzothiazoles and their conjugate systems as potential chemotherapeutics. AREAS COVERED: This review mainly focuses on the structural modifications of benzothiazole scaffold, development of various series of benzothiazoles and their conjugates as new antitumor agents. Furthermore, heterocyclic derivatives bearing benzothiazole moiety and their in vitro as well as in vivo screening, structure-activity relationships (SAR), mechanism, pharmacokinetics, clinical use and their future therapeutic applications are discussed here. EXPERT OPINION: A large number of benzothiazole derivatives discussed here possess potent anticancer activity and can be further developed as drug candidates. Benzothiazole conjugates could also display synergistic effect and still there is a need to use the drug combinations permitting lower dose and development of new generation of drugs. Despite encouraging results that have been observed for their response to tumor in clinical studies, full characterization of their toxicity is further required for their clinical usage as safe drugs for the treatment of cancer. We believe that this review gives a better understanding and scope for future drug design and development of benzothiazole-based compounds to implicate their use in cancer chemotherapy.     

Perspectives on the development of novel potentially active quinolones against tuberculosis and cancer

Quinolones and its derivatives comprise an important group of heterocyclic compounds that exhibit a wide range of pharmacological properties such as antibacterial, antitumor, antiviral, anti-ischemic, antiparasitic and anxiolytic. Persistent efforts have been made over the years to develop novel congeners with superior biological activities and minimal potential for undesirable side-effects. The present review aims to highlight some recent discoveries on the development of novel quinolone-based compounds with potential antitubercular and anticancer activity.