Studies of <i>in vitro</i> anti-prostate cancer potential of newer 1,2,4-triazolo-1,3,4-thiadiazines with different heteroaromatics

Abstract

&lt;p&gt;This study was aimed to evaluate anticancer potential of newer synthesize 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines and its derivatives. All newly furnished scaffolds were subjected to screening for their in vitro anticancer potential against DU-145 and PC-3 prostate cancer cell lines using SRB and MMT bioassays. The structures of final compounds were confirmed with the aid of FT-IR, &lt;sup&gt;1&lt;/sup&gt;H NMR, &lt;sup&gt;13&lt;/sup&gt;C NMR spectroscopy and CHN analysis. Bioassay studies suggested that all thiadiazines were promising cytotoxic agents with % cytotoxicity ranging from 44.39-71.24%, whereas potent GI&lt;sub&gt;50&lt;/sub&gt; level in the range 11.96-32.51 µg/mL and results were comparable to the potencies of control drugs adriamycin and doxorubicin. Variation of heterocyclic pharmacophores along with the C-5 position of 1,2,4-triazole in terms of quinoline, quinazoline, coumarin and pyridine lead to the different SAR predictions in which quinoline and benzimidazole moieties found most promising.&lt;/p&gt;&lt;p&gt; &lt;/p&gt;

Towards anticancer fluoroquinolones: A review article

“…An isothiazole ring fused with the quinolone nucleus at position 2 and 3 was reported to improve the potency . Similar to the antibacterial quinolones, C4 carbonyl was reported to be essential for the activity; other studies revealed that substitution with an alkoxy group as well as substituted amino moieties at position 4 can produce potent anticancer agents . Substitution at position 5 can affect the steric configuration and planarity of the whole compound.…”

Vision on Synthetic and Medicinal Facets of 1,2,4-Triazolo[3,4-b][1,3,4]thiadiazine Scaffold

“…A series 1,2,4-triazolo[3,4- b ][1,3,4]thiadiazines ( 99 ) was prepared by Fan et al [ 70 ] and evaluated for their in vitro anticancer activity against two prostate cancer cell lines PC-3 and DU-145 using SRB (sulforhodamine B) and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. All the synthesized compounds exhibited remarkable cytotoxicity against targeted cell lines with GI 50 values ranging from 12.0 to 32.5 μg ml −1 and 16.5–27.7 μg ml −1 against DU-145 and PC-3 cell lines, respectively.…”

Recent Strategies in Design of Antitumor and Antibacterial Fluoroquinolones

“…Position 4 carbonyl group was essential for quinolones antibacterial activity, substitution at this position abolish the activity [56]. However, other studies revealed that substitution with alkoxy and amino groups at this position gave potent anticancer agents [70,71]. Position 5: Substitutions at this position have a great influence on the planarity and structural configuration of quinolones, as well as, cell permeability and affinity of the drug to bind with the target [72].…”