Abstract
Synthesis of four compounds belonging to mesoionic class, (E)-3-phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium chloride derivatives (5a–d) and their biological evaluation against MT2 and C92 cell lines infected with human T-cell lymphotropic virus type-1 (HTLV-1), which causes adult T-cell leukemia/lymphoma (ATLL), and non-infected cell lines (Jurkat) are reported. The compounds were obtained by convergent synthesis under microwave irradiation and the cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Results showed IC50 values of all compounds in the range of 1.51–7.70 μM in HTLV-1-infected and non-infected cells. Furthermore, it was observed that 5b could induce necrosis after 24 h for Jurkat and MT2 cell lines. The experimental (fluorimetric method) and theoretical (molecular docking) results suggested that the mechanism of action for 5b could be related to its capacity to intercalate into DNA. Moreover, the preliminary pharmacokinetic profile of the studied compounds (5a–d) was obtained through human serum albumin (HSA) binding affinity using multiple spectroscopic techniques (circular dichroism, steady-state and time-resolved fluorescence), zeta potential and molecular docking calculations. The interaction HSA:5a–d is spontaneous and moderate (Ka ~ 104 M−1) via a ground-state association, without significantly perturbing both the secondary and surface structures of the albumin in the subdomain IIA (site I), indicating feasible biodistribution in the human bloodstream.
Highlights
In 2018, Global Cancer Statistics estimated that 18.1 million new cases of cancer and 9.6 million deaths would occur around the world
The aryl-thioureas were prepared from substituted anilines and ammonium irradiation as the power supply
These results clearly show that compound 5a has the highest cytotoxicity value against Human T-cell lymphotropic virus type 1 (HTLV-1) infected cell lines, i.e., MT2 or C91/PL, with IC50 values of 1.51 and 2.82 μM, respectively
Summary
In 2018, Global Cancer Statistics estimated that 18.1 million new cases of cancer and 9.6 million deaths (excluding nonmelanoma skin cancer) would occur around the world. Substituted styryl moiety, important results for in vitro cytotoxic activity in various types of tumor results on the antiviral activityand of 1,3,4-thiadiazole derivatives against which cells,Besides, including leukemias [23,32,33,34], in vivo antitumor effects haveHIV-1 been[37,38,39,40], observed belong to the same Retroviridae family, have been reported in the literature. For the first time the evaluation of 5a–d as promising chemotherapy agents
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