Important chemical structural features of curcumin and its derivatives: How do they influence their anticancer activity?

Curcumin is the active component of the Indian spice turmeric, known since ancient times for medicinal properties. Extensive research in the last two to three decades has confirmed its promising pharmacological properties such as anti-cancer, anti-oxidant, anti-inflammatory etc., leading to several ongoing/completed clinical trials. Curcumin has three reactive functional groups: one diketone moiety, and two phenolic groups. Curcumin interacts with several biomolecules through non-covalent and covalent binding. However, the properties limiting its potential are low bioavailability and fast degradation. The metabolites as well as degradation products of curcumin show biological activities but not as much as curcumin. To overcome these limitations, new analogues with modifications on both o-methoxy group and the diketo structures of curcumin have been developed. Of several analogues, dimethyl curcumin, where the phenolic OH is absent showed better anti-tumor activity. Also, the isoxazole and pyrazole derivatives of curcumin, derivatized at the diketo moiety have been investigated in our group. Hispolon, which is a half curcumin analogue also showed interesting cellular activity. Here in the present manuscript, the comparative cytotoxic effect of curcumin and some of these derivatives in cancer cells is presented. The results indicated that specific structural modifications on curcumin can be adopted to fine-tune its desired anticancer activity

Important chemical structural features of curcumin and its derivatives: How do they influence their anticancer activity?

228-235Curcumin is the active component of the Indian spice turmeric, known since ancient times for medicinal properties. Extensive research in the last two to three decades has confirmed its promising pharmacological properties such as anti-cancer, anti-oxidant, anti-inflammatory etc., leading to several ongoing/completed clinical trials. Curcumin has three reactive functional groups: one diketone moiety, and two phenolic groups. Curcumin interacts with several biomolecules through non-covalent and covalent binding. However, the properties limiting its potential are low bioavailability and fast degradation. The metabolites as well as degradation products of curcumin show biological activities but not as much as curcumin. To overcome these limitations, new analogues with modifications on both o-methoxy group and the diketo structures of curcumin have been developed. Of several analogues, dimethyl curcumin, where the phenolic OH is absent showed better anti-tumor activity. Also, the isoxazole and pyrazole derivatives of curcumin, derivatized at the diketo moiety have been investigated in our group. Hispolon, which is a half curcumin analogue also showed interesting cellular activity. Here in the present manuscript, the comparative cytotoxic effect of curcumin and some of these derivatives in cancer cells is presented. The results indicated that specific structural modifications on curcumin can be adopted to fine-tune its desired anticancer activity

Survival of Civilian and Prisoner Drug-Sensitive, Multi- and Extensive Drug- Resistant Tuberculosis Cohorts Prospectively Followed in Russia

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Collaborative Enhancement of Antibody Binding to Distinct PECAM-1 Epitopes Modulates Endothelial Targeting

Antibodies to platelet endothelial cell adhesion molecule-1 (PECAM-1) facilitate targeted drug delivery to endothelial cells by “vascular immunotargeting.” To define the targeting quantitatively, we investigated the endothelial binding of monoclonal antibodies (mAbs) to extracellular epitopes of PECAM-1. Surprisingly, we have found in human and mouse cell culture models that the endothelial binding of PECAM-directed mAbs and scFv therapeutic fusion protein is increased by co-administration of a paired mAb directed to an adjacent, yet distinct PECAM-1 epitope. This results in significant enhancement of functional activity of a PECAM-1-targeted scFv-thrombomodulin fusion protein generating therapeutic activated Protein C. The “collaborative enhancement” of mAb binding is affirmed in vivo, as manifested by enhanced pulmonary accumulation of intravenously administered radiolabeled PECAM-1 mAb when co-injected with an unlabeled paired mAb in mice. This is the first demonstration of a positive modulatory effect of endothelial binding and vascular immunotargeting provided by the simultaneous binding a paired mAb to adjacent distinct epitopes. The “collaborative enhancement” phenomenon provides a novel paradigm for optimizing the endothelial-targeted delivery of therapeutic agents

From Mendel’s discovery on pea to today’s plant genetics and breeding

In 2015, we celebrated the 150th anniversary of the presentation of the seminal work of Gregor Johann Mendel. While Darwin’s theory of evolution was based on differential survival and differential reproductive success, Mendel’s theory of heredity relies on equality and stability throughout all stages of the life cycle. Darwin’s concepts were continuous variation and “soft” heredity; Mendel espoused discontinuous variation and “hard” heredity. Thus, the combination of Mendelian genetics with Darwin’s theory of natural selection was the process that resulted in the modern synthesis of evolutionary biology. Although biology, genetics, and genomics have been revolutionized in recent years, modern genetics will forever rely on simple principles founded on pea breeding using seven single gene characters. Purposeful use of mutants to study gene function is one of the essential tools of modern genetics. Today, over 100 plant species genomes have been sequenced. Mapping populations and their use in segregation of molecular markers and marker–trait association to map and isolate genes, were developed on the basis of Mendel's work. Genome-wide or genomic selection is a recent approach for the development of improved breeding lines. The analysis of complex traits has been enhanced by high-throughput phenotyping and developments in statistical and modeling methods for the analysis of phenotypic data. Introgression of novel alleles from landraces and wild relatives widens genetic diversity and improves traits; transgenic methodologies allow for the introduction of novel genes from diverse sources, and gene editing approaches offer possibilities to manipulate gene in a precise manner