Synthesis and characterization of novel combretastatin analogues of 1,1-diaryl vinyl sulfones, with antiproliferative potential via in-silico and in-vitro studies.

Novel 1,1-diaryl vinyl-sulfones analogues of combretastatin CA-4 were synthesized via Suzuki-Miyaura coupling method and screened for in-vitro antiproliferative activity against four human cancer cell lines: MDA-MB 231(breast cancer), HeLa (cervical cancer), A549 (lung cancer), and IMR-32 (neuroblast cancer), along with a normal cell line HEK-293 (human embryonic kidney cell) by employing 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The compounds synthesised had better cytotoxicity against the A549 and IMR-32 cell lines compared to HeLa and MDA-MB-231 cell lines. The synthesized compounds also showed significant activity on MDA-MB-231 cancer cell line with IC50 of 9.85-23.94 µM, and on HeLa cancer cell line with IC50 of 8.39-11.70 µM relative to doxorubicin having IC50 values 0.89 and 1.68 µM respectively for MDA-MB-231 and HeLa cell lines. All the synthesized compounds were not toxic to the growth of normal cells, HEK-293. They appear to have a higher binding affinity for the target protein, tubulin, PDB ID = 5LYJ (beta chain), relative to the reference compounds, CA4 (- 7.1 kcal/mol) and doxorubicin (- 7.2 kcal/mol) except for 4E, 4M, 4N and 4O. The high binding affinity for beta-tubulin did not translate into enhanced cytotoxicity but the compounds (4G, 4I, 4J, 4M, 4N, and 4R, all having halogen substituents) that have a higher cell permeability (as predicted in-silico) demonstrated an optimum cytotoxicity against the tested cell lines in an almost uniform manner for all tested cell lines. The in-silico study provided insight into the role that cell permeability plays in enhancing the cytotoxicity of this class of compounds and as potential antiproliferative agents.

Corrigendum to "Antidiabetic, antioxidant and antimicrobial activities of extracts of Tephrosia bracteolata leaves" [Heliyon 5 (8) (August 2019) e02275].

[This corrects the article DOI: 10.1016/j.heliyon.2019.e02275.].

Antidiabetic, antioxidant and antimicrobial activities of extracts of Tephrosia bracteolata leaves.

AIMS: Plant extracts have long been used for the ethnomedical treatment of diabetes, microbial infections and as a source of antioxidant. This study was aimed at investigating the antidiabetic, antioxidant, and antimicrobial activities of the n-hexane and ethyl acetate extract of Tephrosia bracteolata leaves (TBL) as associated with the ethnobotanical knowledge of the local people of Nigeria. MAIN METHODS: The phytochemical composition of the n-hexane and ethyl acetate extract of the leaves of T. bracteolata were determined following standard procedures in literature, and it's in vitro inhibitory activities against α-glucosidase enzyme. 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS.+) and 1,1-diphenyl-2-picrylhydrazyl (DPPH+) antioxidant activities were also examined. Well diffusion method was employed in evaluating the antimicrobial property of the extracts. KEY FINDINGS: The ethyl acetate extract of T. bracteolata leaves had the greatest inhibitory effect on α-glucosidase, followed by the n-hexane with IC50 43.95 µg/ml and IC50 ˃50 µg/ml respectively. The ethyl acetate also exhibited significant DPPH+ and ABTS.+ antioxidant activity with IC50 of 24.96 µg/ml and 6.48 µg/ml as compared to Ascorbic acid and Trolox (12.24 µg/ml and 5.91 µg/ml) respectively. The zones of inhibition of the ethyl acetate extract of T. bracteolata leaves ranges from 10 - 25 mm at a concentration of 6.25-200 mg/ml, and it showed a greater antibacterial activity than the n-hexane extract, having a zone of inhibition from 10 - 20 mm at concentration of 12.5-200 mg/ml when compared to the standard Gentamycin. Similarly, the ethyl acetate extract of T. bracteolata showed a better anti fungi activity at concentration range 12.5-200 mg/ml than the n-hexane extract at concentration range of 25-200 mg/ml with reference to Tioconazole. These results indicated for the first time that the ethyl acetate extract of T. bracteolata leaves extracts exerted potent inhibitory effects against α-glucosidase, actively scavenge DPPH+ and ABTS.+ free radicals and successfully inhibits the proliferation of Gram positive and Gram negative microorganism. SIGNIFICANCE: TBL is an important source of antidiabetic, antimicrobial and antioxidant agent.