Synthesis and exploration of novel curcumin analogues as anti-malarial agents

Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Recent studies have indicated that curcumin inhibits chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) Plasmodium falciparum growth in culture with an IC50 of not, vert, similar3.25 μM (MIC = 13.2 μM) and IC50 4.21 μM (MIC = 14.4 μM), respectively. In order to expand their potential as anti-malarials a series of novel curcumin derivatives were synthesized and evaluated for their ability to inhibit P. falciparum growth in culture. Several curcumin analogues examined show more effective inhibition of P. falciparumgrowth than curcumin. The most potent curcumin compounds 3, 6, and 11 were inhibitory for CQ-S P. falciparum at IC50 of 0.48, 0.87, 0.92 μM and CQ-R P. falciparum at IC50 of 0.45 μM, 0.89, 0.75 μM, respectively. Pyrazole analogue of curcumin (3) exhibited sevenfold higher anti-malarial potency against CQ-S and ninefold higher anti-malarial potency against CQ-R. Curcumin analogues described here represent a novel class of highly selective P. falciparum inhibitors and promising candidates for the design of novel anti-malarial agents.

Synthesis and exploration of novel curcumin analogues as anti-malarial agents

Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Recent studies have indicated that curcumin inhibits chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) Plasmodium falciparum growth in culture with an IC50 of similar to 3.25 mu M (MIC = 13.2 mu M) and IC50 4.21 mu M (MIC = 14.4 mu M), respectively. In order to expand their potential as anti-malarials a series of novel curcumin derivatives were synthesized and evaluated for their ability to inhibit P. falciparum growth in culture. Several curcumin analogues examined show more effective inhibition of P. falciparum growth than curcumin. The most potent curcumin compounds 3, 6, and 11 were inhibitory for CQ-S P. falciparum at IC50 of 0.48, 0.87, 0.92 mu M and CQ-R P. falcipartan at IC50 of 0.45 mu M, 0.89, 0.75 mu M, respectively. Pyrazole analogue of curcumin (3) exhibited sevenfold higher anti-malarial potency against CQ-S and ninefold higher anti-malarial potency against CQ-R. Curcumin analogues described here represent a novel class of highly selective P. falcipartan inhibitors and promising candidates for the design of novel anti-malarial agents. (C) 2007 Elsevier Ltd. All rights reserved.

Construction of Bis-pyrazole Based Co(II) Metal-Organic Frameworks and Exploration of Their Chirality and Magnetic Properties

In continuation of our interest in pyrazole based multifunctional metal-organic frameworks (MOFs), we report herein the construction of a series of Co(II) MOFs using a bis-pyrazole ligand and various benzene polycarboxylic acids. Employment of different acids has resulted in different architectures ranging from a two-dimensional grid network, porous nanochannels with interesting double helical features such as supramolecular chicken wire, to three-dimensional diamondoid networks. One of the distinguishing features of the network is their larger dimensions which can be directly linked to a relatively larger size of the ligand molecule. Conformational flexibility of the ligand also plays a decisive role in determining both the dimensionality and topology of the final structure. Furthermore, chirality associated with helical networks and magnetic properties of two MOFs have also been investigated.

Mining Unit Tests for Discovery and Migration of Math APIs

Today's programming languages are supported by powerful third-party APIs. For a given application domain, it is common to have many competing APIs that provide similar functionality. Programmer productivity therefore depends heavily on the programmer's ability to discover suitable APIs both during an initial coding phase, as well as during software maintenance. The aim of this work is to support the discovery and migration of math APIs. Math APIs are at the heart of many application domains ranging from machine learning to scientific computations. Our approach, called MATHFINDER, combines executable specifications of mathematical computations with unit tests (operational specifications) of API methods. Given a math expression, MATHFINDER synthesizes pseudo-code comprised of API methods to compute the expression by mining unit tests of the API methods. We present a sequential version of our unit test mining algorithm and also design a more scalable data-parallel version. We perform extensive evaluation of MATHFINDER (1) for API discovery, where math algorithms are to be implemented from scratch and (2) for API migration, where client programs utilizing a math API are to be migrated to another API. We evaluated the precision and recall of MATHFINDER on a diverse collection of math expressions, culled from algorithms used in a wide range of application areas such as control systems and structural dynamics. In a user study to evaluate the productivity gains obtained by using MATHFINDER for API discovery, the programmers who used MATHFINDER finished their programming tasks twice as fast as their counterparts who used the usual techniques like web and code search, IDE code completion, and manual inspection of library documentation. For the problem of API migration, as a case study, we used MATHFINDER to migrate Weka, a popular machine learning library. Overall, our evaluation shows that MATHFINDER is easy to use, provides highly precise results across several math APIs and application domains even with a small number of unit tests per method, and scales to large collections of unit tests.

An overview of recent advances in structural bioinformatics of protein-protein interactions and a guide to their principles

Rich data bearing on the structural and evolutionary principles of protein protein interactions are paving the way to a better understanding of the regulation of function in the cell. This is particularly the case when these interactions are considered in the framework of key pathways. Knowledge of the interactions may provide insights into the mechanisms of crucial `driver' mutations in oncogenesis. They also provide the foundation toward the design of protein protein interfaces and inhibitors that can abrogate their formation or enhance them. The main features to learn from known 3-D structures of protein protein complexes and the extensive literature which analyzes them computationally and experimentally include the interaction details which permit undertaking structure-based drug discovery, the evolution of complexes and their interactions, the consequences of alterations such as post-translational modifications, ligand binding, disease causing mutations, host pathogen interactions, oligomerization, aggregation and the roles of disorder, dynamics, allostery and more to the protein and the cell. This review highlights some of the recent advances in these areas, including design, inhibition and prediction of protein protein complexes. The field is broad, and much work has been carried out in these areas, making it challenging to cover it in its entirety. Much of this is due to the fast increase in the number of molecules whose structures have been determined experimentally and the vast increase in computational power. Here we provide a concise overview. (C) 2014 Elsevier Ltd. All rights reserved.

Phytomedicinal importance of Saraca asoca (Ashoka): an exciting past, an emerging present and a promising future

Since the dawn of civilization, natural resources have remained the mainstay of various remedial approaches of humans vis-a-vis a large number of illnesses. Saraca asoca (Roxb.) de Wilde (Saraca indica L.) belonging to the family Caesalpiniaceae has been regarded as a universal panacea in old Indian Ayurvedic texts and has especially been used to manage gynaecological complications and infections besides treating haemmorhagic dysentery, uterine pain, bacterial infections, skin problems, tumours, worm infestations, cardiac and circulatory problems. Almost all parts of the plant are considered pharmacologically valuable. Extensive folkloric practices and ethnobotanical applications of this plant have even lead to the availability of several commercial S. asoca formulations recommended for different indications though adulteration of these remains a pressing concern. Though a wealth of knowledge on this plant is available in both the classical and modern literature, extensive research on its phytomedicinal worth using state-of-the-art tools and methodologies is lacking. Recent reports on bioprospecting of S. asoca endophytic fungi for industrial bioproducts and useful pharmacologically relevant metabolites provide a silver lining to uncover single molecular bio-effectors from its endophytes. Here, we describe socio-ethnobotanical usage, present the current pharmacological status and discuss potential bottlenecks in harnessing the proclaimed phytomedicinal worth of this prescribed Ayurvedic medicinal plant. Finally, we also look into the possible future of the drug discovery and pharmaceutical R&D efforts directed at exploring its pharma legacy.