Synthesis, biological evaluation, and molecular docking of novel 1,3,4-substituted-thiadiazole derivatives as potential anticancer agent.

In an attempt to develop potent anti-cancer agents, a new 1,3,4-substituted-thiadiazole derivatives (8b-g), starting from 4-substituted-thiazol-2-chloroacetamides (4b-g), were synthesized and evaluated for their cytotoxic effects on multiple human cancer cell lines, including the hepatocellular carcinoma (HEPG-2), human lung carcinoma (A549), human breast carcinoma (MCF-7) and pseudo-normal human embryonic liver (L02) cancer cell lines by an MTT assay. Among all synthesized compounds, compound 8d showed the potent anti-cancer activities with GI50 values of 2.98, 2.85 and 2.53 µM against MCF-7, A549 and HepG-2 cell lines respectively as compared to standard drug Doxorubicin. Furthermore, molecular modelling studies have spotlighted the anchoring role of 1,3,4-substituted-thiadiazole moiety in bonding and hydrophobic interaction with the key amino acid residues. Therefore, these results can provide promising starting points for further development of best anti-cancer agents.

Synthesis, Biological and Molecular Docking Studies of Thiazole-Thiadiazole derivatives as potential Anti-Tuberculosis Agents.

Tuberculosis remains a global health threat, with increasing infection rates and mortality despite existing anti-TB drugs. The present work focuses on the research findings regarding the development and evaluation of thiadiazole-linked thiazole derivatives as potential anti-tuberculosis agents. We present the synthesis data and confirm the compound structures using spectroscopic techniques. The current study reports twelve thiazole-thiadiazole compounds (5 a-5 l) for their anti-tuberculosis and related bioactivities. This paper emphasizes compounds 5 g, 5 i, and 5 l, which exhibited promising MIC values, leading to further in silico and interaction analysis. Pharmacophore mapping data included in the present analysis identified tubercular ThyX as potential drug targets. The compounds were evaluated for anti-tubercular activity using standard methods, revealing significant MIC values, particularly compound 5 l, with the best MIC value of 7.1285 µg/ml. Compounds 5 g and 5 i also demonstrated moderate to good MIC values against M. tuberculosis (H37Ra). Structural inspection of the docked poses revealed interactions such as hydrogen bonds, halogen bonds, and interactions containing Pi electron cloud, shedding light on conserved interactions with residues like Arg 95, Cys 43, His 69, and Arg 87 from the tubercular ThyX enzyme.

Synthesis and Functionalization of Coumarin-Pyrazole Scaffold: Recent Development, Challenges, and Opportunities.

Heterocycles are the main structural motif of DNA and RNA and play a crucial role in various chemical reactions of metabolisms. Therefore, heterocyclic compounds show good physiological and pharmacological properties. Coumarin and pyrazole scaffolds are present in many commercial drug molecules and natural products. This review overviews the progress made in the synthesis and functionalization of the coumarin- pyrazole hybrid heterocycle. It also includes discussion on the possible reactive sites of heterocycles, functionalization, and mechanistic pathways to incorporate pyrazole pharmacophore unit in synthesis. Several synthesis and biological studies reveal that the combination of the coumarin-pyrazole moiety is a prominent structural motif to find lead compounds in drug discovery.

Role of amphiphilic [metal:chelator] complexes in a non-chromatographic antibody purification platform.

We have recently introduced a non-chromatographic alternative for antibody (Ab) purification, one which does not require the use of Protein A. With this approach, polyclonal human or mouse immunoglobulins (IgG's) are captured almost quantitatively by Tween-20 micelles conjugated with a [chelator:divalent metal cation] complex. Target IgG structure remains native even following extraction from the surfactant aggregate. In the present work, we explore the effect of varying both components of the [metal:chelator] pair on the yield of purified Ab. Capture efficiency is observed to correlate with the formation of sufficiently large detergent aggregates, as determined by dynamic light scattering (DLS) and polyacrylamide gel electrophoresis (PAGE). This, in turn, depends on the rigidity and aromaticity of the chelator. Detergent aggregates are stable over a wide range of pH values (pH = 3-9). Under acidic conditions (3-3.8) they lead to good IgG recovery yields (70-78%) with purity similar to that obtained with Protein A chromatography while maintaining the monomeric state of the IgG's. Finally, the influence of the environment and the presence of various water-soluble chelators (e.g. EDTA, histidine, imidazole) on process efficiency, is described.

Membrane protein crystallization in micelles conjugated by nucleoside base-pairing: A different concept.

The dearth of high quality, three dimensional crystals of membrane proteins, suitable for X-ray diffraction analysis, constitutes a serious barrier to progress in structural biology. To address this challenge, we have developed a new crystallization medium that relies on the conjugation of surfactant micelles via base-pairing of complementary hydrophobic nucleosides. Base-pairs formed at the interface between micelles bring them into proximity with each other; and when the conjugated micelles contain a membrane protein, crystal nucleation centers can be stabilized, thereby promoting crystal growth. Accordingly, two hydrophobic nucleoside derivatives - deoxyguanosine (G) and deoxycytidine (C), each covalently bonded to a 10 carbon chain were synthesized and added to an aqueous solution containing octyl ß-d-thioglucopyranoside micelles. These hydrophobic nucleosides induced the formation of oil-rich globules after 2days incubation at 19°C or after a few hours in the presence of ammonium sulfate; however, phase separation was inhibited by 100mM GMP. The presence of the membrane protein bacteriorhodopsin in the conjugated - micellar dispersion resulted in the growth within the colorless globules of a variety of purple crystals, the color indicating a functional protein. On this basis, we suggest that conjugation of micelles via base-pair complementarity may provide significant assistance to the structural determination of integral membrane proteins.

Diacetoxyiodobenzene mediated one-pot synthesis of diverse carboxamides from aldehydes.

A novel, one-pot, and highly facile protocol has been devised for an easy access of a series of novel glycosyl carboxamides from aldehydes using diacetoxyiodobenzene in the presence of ionic liquid at ambient temperature.

Facile route for N 1-aryl benzotriazoles from diazoamino arynes via CuI-mediated intramolecular N-arylation.

A facile and high-yielding protocol for diverse benzotriazoles through intramolecular N-arylation of different o-chloro-1,2,3-benzotriazenes using CuI/Cs2CO3 has been developed.

Alkaloids: future prospective to combat leishmaniasis.

Leishmaniasis, a vector-borne parasitic disease resulting from infection of macrophages by obligate intracellular parasites of genus Leishmania, has been considered a major tropical disease by the World Health Organization. Generic pentavalent antimonials have been the mainstay for therapy in the endemic regions because of its efficacy and cost effectiveness. However, the growing incidence of resistance for the pentavalent antimony complex in endemic and non-endemic regions has seriously hampered their use in these regions. The second line drugs such as amphotericin B, paromomycin and miltefosine are the other alternatives, but they merely fulfill the desired requirements of a safe drug. The recent researches focused on plants have shown a wise way to get a true and potentially rich source of drug candidates against leishmaniasis, where alkaloids have been found more effective. The present review initially highlights the current status of leishmaniasis, synergy of the disease with HIV, therapeutic options available and in later sections summarizes all alkaloids, which have shown significant antileishmanial activities.