Synthesis, in silico pharmacokinetic analysis and anticancer activity evaluation of benzothiazole-triazole hybrids

Over the past decade, a variety of benzothiazole derivatives have been reported with promising anticancer activity. Benzothiazole and its analogues are capable of acting on a number of molecular targets and thus exerting their anticancer activity. To further develop benzothiazole derivatives as anticancer agents, we attempted to design and synthesize a library of benzothiazole-triazole derivatives. The synthesized hybrid compounds have been selected by National Cancer Institute, USA for the in vitro activity evaluation against 60 human cancer cell lines in a one dose screening panel. Most of the synthesized compounds showed 60-80% growth rate against renal cancer cell line UO-31

Ionic liquids: a versatile medium for palladium-catalyzed reactions

A number of carbon-carbon bond forming reactions in organic chemistry (such as the Heck, Suzuki, Stille, Negishi, Sonogashira coupling etc) are facilitated by catalysis with palladium compounds. An attempt has been made to present a detailed and comprehensive literature collection about the versatility of ionic liquid in conjunction with palladium for various types of reactions

Synthesis of 1,3,4-oxadiazole and imidazo[1,2-a]pyridine based molecular hybrids and their in vitro antituberculosis and cytotoxicity studies

1005-1018A library of novel 1,3,4-oxadiazole substituted imidazo[1,2-a]pyridine based molecular hybrids have been synthesized and evaluated against Mycobacterium tuberculosis H37Rv. Out of 59 compounds synthesized, ten compounds show activity in the range of 3.125-12.5 μM. Compound 8p is found to be most active with MIC99 value of 3.125-6.25 μM. Further, these ten compounds have also been tested for their toxicity against THP-1 cell line and are found to be non-toxic with TC50 value in the range of (10 - >50 μM) concentration

Synthesis and antibacterial/antitubercular activity evaluation of symmetrical <i style="mso-bidi-font-style:normal">trans</i>-cyclohexane-1,4-diamine derivatives

1441-1450<span style="font-size:12.0pt;font-family: " times="" new="" roman";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-gb;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="" lang="EN-GB">A library of symmetrical trans-cyclohexane-1,4-diamine derivatives have been synthesized and evaluated for their activity against the M. tb H37Rv strain. Most of the synthesized compounds show moderate to weak activity against M. tb H37Rv strain. Out of twenty-seven compounds tested, four compounds having substitution at p-position on the aromatic ring exhibit activity with MIC99 value ranging from 12.5 - 25 µM. Compound 9u having i-propyl group substitution at p-position is found to be the most potent among all the tested compounds with MIC99 value of 12.5 µM against M. tb H37Rv strain. All these compounds have also been tested against <i style="mso-bidi-font-style: normal">Methicilin resistant Staphylococcus aureus (MRSA), and four of the compounds <b style="mso-bidi-font-weight: normal">9c, 9i, 9p and 9s possess good antibacterial activity with IC50 ranging from 128 mg/L – 256 mg/L.</span

The competence of 7,8-diacetoxy-4-methylcoumarin and other polyphenolic acetates in mitigating the oxidative stress and their role in angiogenesis

The potential role of polyphenolic acetate (PA) in causing diverse biological and pharmacological actions has been well studied in our laboratory. Our investigations, for the first time, established the role of calreticulin transacetylase (CRTAase) in catalyzing the acetylation of nitric oxide synthase (NOS) by Pas leading to robust activation of NOS. 7, 8-Diacetoxy-4-methylcoumarin (DAMC) and other acetoxycoumarins augmented the expression of thioredoxin (TRX) and vascular endothelial growth factor (VEGF) in human peripheral blood mononuclear cells (PBMCs). These findings substantiated our earlier observations that DAMC was a superb inducer of angiogenesis. The enhanced expression of thioredoxin reductase (TRXR) and diminished expression of thioredoxin interacting protein (TRXIP) leading to increased expression and activity of TRX in PBMCs due to the action of DAMC was revealed by real time RT-PCR analysis. The possible activation of TRX due to acetylation was confirmed by the fact that TRX activity of PBMCs was enhanced by variousacetoxycoumarins in tune with their affinities to CRTAase as substrates. DAMC caused enhanced production of NO by way of acetylation of NOS as mentioned above and thereby acted as an inducer of VEGF. Real time RT-PCR and VEGF ELISA results also revealed the overexpression of TRX. DAMC and other PAs were found to reduce the oxidative stress in cells as proved by significant reduction of intracellular ROS levels. Thus, the crucial role of TRX in DAMC-induced angiogenesis with the involvement of VEGF was established