Synthesis of benzo[d]imidazo[2,1-b]thiazole-chalcone conjugates as microtubule targeting and apoptosis inducing agents.

A series of benzo[d]imidazo[2,1-b]thiazole-chalcone conjugates (5a-aa) were designed, synthesized and evaluated for their cytotoxic potency against a panel of human cancer cell lines like lung (A-549), breast (MDA MB-231), prostrate (DU-145) and colon cancer (HT-29). Preliminary results revealed that some of these conjugates like 5d and 5u exhibited significant antiproliferative effect against human breast cancer (MDA MB-231) with IC50 values of 1.3 and 1.2 µM respectively. To investigate the mechanistic aspects underlying the activity, the detailed biological studies of these promising conjugates (5d and 5u) were carried out on the MDA MB-231 cancer cells. Flow cytometric analysis revealed that these conjugates induce cell-cycle arrest in the G2/M phase. The tubulin polymerization assay suggests that these conjugates effectively inhibit microtubule assembly. In addition, morphological changes, reactive oxygen species (ROS) detection by 2', 7'-dichlorofluorescin diacetate (DCFDA) and annexin V-FITC/PI assays indicate that 5d and 5u induces apoptosis. Furthermore, in silico computational studies, including molecular docking studies have been carried out to rationalise the binding modes of these conjugates with the tubulin protein.

PHYTOCHEMICAL, PHARMACOLOGICAL AND BIOLOGICAL PROFILES OF TRAGIA SPECIES (FAMILY: EUPHORBIACEAE).

BACKGROUND: Tragia belongs to the family Euphorbiaceae which contains about 152 species. Interestingly, most of the earlier investigations have been done using only five Tragia species, namely, Tragia involucrata, Tragia cannabina, Tragia spathulata, Tragia plukenetii, and Tragia benthamii. The objective of the present review is to compile the phytochemical, pharmacological and biological studies of the selected five Tragia species reported in the literature. METHODS: The reported data/information was retrieved mainly from the online databases of PubMed (MEDLINE), EMBASE and Botanical Survey of India. RESULTS: The present review elaborated the phytochemical, pharmacological and biological properties of the selected five Tragia species obtained from recent literature. CONCLUSION: This review provides a basis for future investigation of Tragia species and, especially for those species that have not been explored for biological and pharmacological activities.

Design, Synthesis, and Immunological Evaluation of Benzyloxyalkyl-Substituted 1,2,3-Triazolyl α-GalCer Analogues.

Replacement of the amide moiety in the structure of α-GalCer with a 1,2,3-triazole linker is known to elicit a response skewed toward Th2 immunity, and glycolipids containing an aromatic ring in the terminus of their acyl or phytosphingosine structural component exhibit an enhanced Th1 immune response. In the current study, synthesis and immunological screening of a focused library of benzyloxyalkyl-substituted 1,2,3-triazolyl α-GalCer analogues are reported. The novel α-GalCer analogues activate invariant natural killer T (iNKT) cells via CD1d mediated presentation, which was confirmed by in vitro tests performed on iNKT hybridomas incubated with CD1d proteins. When tested on isolated murine splenocytes, the T1204B and T1206B compounds stimulated higher levels of both IFN-γ and IL-4 cytokine expression in vitro compared to that of α-GalCer.

Design, synthesis and immunological evaluation of 1,2,3-triazole-tethered carbohydrate-Pam3Cys conjugates as TLR2 agonists.

Novel triazolyl Pam3Cys conjugates encompassing various carbohydrate entities have been synthesized by copper mediated azide-alkyne click chemistry protocol with a view to probe the SAR pertaining to their adjuvant activity in conjunction with OVA as antigen. The preliminary ex vivo cytokine profiling revealed optimal Th1 activation and the in vivo adjuvant studies of ribose derived hybrid (6 e) revealed a marked improvement in the OVA specific antibody IgG response and Th1 cytokine expressions. The triazolyl Pam3Cys carbohydrate conjugates were found to be the hTLR2 agonists as revealed by their SEAP activity due to NFKB activation. The described protocol is the first successful attempt of the amalgamation of carbohydrate-Pam3Cys motifs tethered to a triazole linker as a peptide free adjuvant.