Cinnamic acid and its phenolic analogues are natural substances. Chemically, in cinnamic acids the 3-phenyl acrylic acid functionality offers three main reactive sites; substitution at the phenyl ring, addition at the α,β- unsaturation and the reactions of the carboxylic acid functionality. Owing to these chemical aspects cinnamic acid derivatives received much attention in medicinal research as traditional as well as recent synthetic antitumor agents. We observed that in spite of their rich medicinal tradition, cinnamic acid derivatives and their anticancer potentials remained underutilized for several decades since the first published clinical use in 1905. In last two decades, there has been huge attention towards various cinnamoyl derivatives and their antitumor efficacy. This review provides a comprehensive and unprecedented literature compilation concerning the synthesis and biological evaluation of various cinnamoyl acids, esters, amides, hydrazides and related derivatives in anticancer research. We envisage that our effort in this review contributes a much needed and timely addition to the literature of medicinal research.

A vertical jet of water impinging on a horizontal surface produces a radial film flow followed by a circular hydraulic jump. We report a phenomenon where fairly large (1 ml) drops of liquid levitate just upstream of the jump on a thin air layer between the drop and the film flow. We explain the phenomenon using lubrication theory. Bearing action both in the air film and the water film seems to be necessary to support large drops. Horizontal support is given to the drop by the hydraulic jump. A variety of drop shapes is observed depending on the volume of the drop and liquid properties. We show that interaction of the forces due to gravity, surface tension, viscosity and inertia produces these various shapes.

Tuberculosis, HIV coinfection with TB, emergence of multidrug-resistant TB, and extensively drug-resistant TB are the major causes of death from infectious diseases worldwide. Because no new drug has been introduced in the last several decades, new classes of molecules as anti-TB drugs are urgently needed. Herein, we report the synthesis and structure-activity relationships of a series of thioester, amide, hydrazide, and triazolophthalazine derivatives of 4-alkoxy cinnamic acid. Many compounds exhibited submicromolar minimum inhibitory concentrations against Mycobacterium tuberculosis strain (H(37)Rv). Interestingly, compound 13e, a 4-isopentenyloxycinnamyl triazolophthalazine derivative, was found to be 100-1800 times more active than isoniazid (INH) when tested for its ability to inhibit the growth of INH-resistant M. tuberculosis strains. The results also revealed that 13e does not interfere with mycolic acid biosynthesis, thereby pointing to a different mode of action and representing an attractive lead compound for the development of new anti-TB agents.

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Globally, tuberculosis is slowly declining each year and it is estimated that 37 million lives were saved between 2000 and 2013 through effective diagnosis and treatment. Currently, diagnosis relies on demonstration of the bacteria, Mycobacterium tuberculosis (Mtb), in clinical specimens by serial sputum microscopy, culture and molecular testing. Commercial immunoassay lateral flow kits developed to detect Mtb lipoglycan lipoarabinomannan (LAM) in urine as a marker of active TB exhibit poor sensitivity, especially in immunocompetent individuals, perhaps due to low abundance of the analyte. Our present study was designed to develop methods to validate the presence of LAM in a quantitative fashion in human urine samples obtained from culture-confirmed TB patients. Herein we describe, a consolidated approach for isolating LAM from the urine and quantifying D-arabinose as a proxy for LAM, using Gas Chromatography/Mass Spectrometry. 298 urine samples obtained from a repository were rigorously analyzed and shown to contain varying amounts of LAM-equivalent ranging between ~10–40 ng/mL. To further substantiate that D-arabinose detected in the samples originated from LAM, tuberculostearic acid, the unique 10-methyloctadecanoic acid present at the phosphatidylinositol end of LAM was also analyzed in a set of samples and found to be present confirming that the D-arabinose was indeed derived from LAM. Among the 144 samples from culture-negative TB suspects, 30 showed presence of D-arabinose suggesting another source of the analyte, such as disseminated TB or from non-tuberculosis mycobacterium. Our work validates that LAM is present in the urine samples of culture-positive patients in small but readily detectable amounts. The study further substantiates LAM in urine as a powerful biomarker for active tuberculosis.

Mycobacterium tuberculosis lipoarabinomannan (LAM) is a biomarker for active TB disease. The presence of LAM in urine of TB patients, whether HIV positive or negative has been validated by a gas chromatography/mass spectral method with good specificity (84%) and sensitivity (99%). However, point-of-care (POC) methods to detect TB LAM in urine using immunoassays have poor sensitivity and are limited to only HIV co-infected TB diagnosis. We hypothesized that these disappointing results with the POC methods may be due to the antibodies used in the immunoassays as there could be structural differences between LAM in vivo vs. LAM in vitro. To address this issue, we infected C3HeB/FeJ mice with M.tb W. Beijing SA161, and purified LAM from the lung. Analysis of these sources of LAM using a panel of existing mAbs revealed differences in epitope patterns. Conventionally, the non-reducing termini of LAM are identified by their release with endoarabinanase. These epitopes correspond to linear tetra-(Ara 4 ), a branched hexa-(Ara 6 ) arabinofuranosides and their mannose-capped versions. We discovered two distinct epitopes. In the first case it was found that the non-reducing termini of LAM from M.tb strain SA161 are highly succinylated, especially when the LAM was isolated from the mouse lungs. In the second case it was found that Cellulomonas endoarabinanase digestion of LAM from both SA161 and LAM from a TB+ HIV-patient's urine yielded epitopes based on 5 arabinoses as major components and a profound lack of Ara 6 . The epitopes based on 5 arabinoses from M.tb SA161and from the LAM in human urine must result from underlying structural and thus epitope differences. These results suggest approaches to develop specific antibodies for POC tests for LAM in urine of suspected TB patients.

NCT02771249.