Current Bioactive Compounds - Volume 3, Issue 1, 2007

Structural diversity is the most important fundamental in the modern drug discovery program. Every structural type, in principal, is capable of locking a particular disease mechanism. Everyday in various laboratories of the world, thousands of structurally diverse compounds are synthesized or isolated from natural sources. This structural diversity, if properly harnessed, can lead to breakthrough discoveries and improve, currently dismal, efficiency in drug development. One of the reasons why combinatorial chemistry has not been as successful as expected in delivering the novel molecular entities, is inherently the low structural diversity of resulting synthetic libraries. Medicinal chemists and other researchers involved in drug discovery programs, therefore always look for novel structural leads with potential to be used against specific biological targets. The quarterly journal, “Current Bioactive Compounds (CBC)”, thus provides an important first set of information for drug discovery scientists. We are glad that the journal has been very well received globally and has already achieved a substantial subscription base in the last two years. Along with easy-to-read directory of newly discovered bioactive compounds, in-depth selected reviews on various classes of bioactive compounds have also been included in this issue of CBC. These reviews, contributed by leading scientists in their fields, focus on structures and mechanisms of action of various classes most important of bioactive chemical compounds against a range of most important of biological disorders. At the end, we wish to acknowledge the contributions of the dedicated editorial and secretarial staff of the Bentham Science Publishers. Notable among them are Mr. Mahmood Alam (Director Publications) and his team, Dr. Ziaullah, Miss Samreen Laeeq and Mr. Ansar Ahmed Qadri.

In this review we cover the structures, occurrence, biological activities and synthesis of all the spongianes and rearranged spongianes since their discovery in 1974. We have given special attention to structure revisions and biological properties of these polycyclic terpenoids of exclusive marine origin. However, an important part of the review describes the synthetic efforts in the field. Thus, this part has been subdivided into syntheses from other natural products, syntheses by biomimetic approaches and other approaches including enantioselective total syntheses.

Podophyllotoxin is a naturally occurring lignan with important antineoplastic and antiviral properties and supported by detailed understanding of their mechanism of action, and facilitated by chemical manipulations that have amplified their bioactivity, the podophyllotoxin analogues have advanced to the forefront of several areas of therapeutic and developmental chemotherapy. Additive and synergistic laboratory interactions with other cytotoxic drugs have been exploited to allow development of podophyllotoxin-based multidrug regimens, which are showing important activity in several malignancies, and many of its related analogues will complement conventional pharmaceuticals in treatment, prevention and diaganosis of disease, while at the same time adding value to agriculture. Additive and synergistic laboratory interactions with other cytotoxic drugs have been exploited to allow development of etoposide-based multidrug regimens, which are showing important activity in several malignancies. Extensive structural modifications of podophyllotoxin have been performed in order to obtain more potent and less toxic antitumour agents, which resulted in the widespread clinical introduction of two semisynthetic glucoconjugate analogues of etoposide and teniposide and newer agents with promising preclinical activity are in various stages of clinical assessment. As knowledge of molecular and biochemical mechanisms of action and resistance continues to expand, newer and better podophyllotoxin-based strategies for treatment of malignant disease are likely to evolve. This review provides a detailed discussion of research advances in the synthetic and medicinal chemistry of podophyllotoxin, and addresses the short history and pharmacological action of these compounds and further outlines the preclinical development and clinical trials of drugs in the pipeline and marketing approval. Finally, a systemic evaluation of novel and important analogues of podophyllotoxin and their contribution to the current structure-activity profile are considered. It is hoped that this review will be able to address the contributions of podophyllotoxin-related research to overall drug discovery and development and the role that this field will play in future.

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