New 1,3,4-thiadiazoles as potential anticancer agents: pro-apoptotic, cell cycle arrest, molecular modelling, and ADMET profile

Abstract

Compound 19 arrested the MCF-7 cells at the G2/M phase probably through inhibition of CDK1 and elicited apoptosis. It did not violate Lipinski's rule of five and has a low blood brain barrier penetration and high intestinal absorption.

Synthesis and evaluation of larvicidal efficacy against C. pipiens of some new heterocyclic compounds emanated from 2‐cyano‐N′‐(2‐(2,4‐dichlorophenoxy)acetyl)acetohydrazide

“…Based on our previous work, [17,[19][20][21][22][23][24][25][26][27][28][29] which encouraged us to design a novel cyanoacetohydrazide including chlorine motif to enhance the insecticidal activity of the synthesized compounds. Outset, treatment of 2-(2,4-dichlorophenoxy)acetyl chloride (1) with cyanoacetohydrazide (2) in dry acetonitrile at ambient temperature under stirring system afforded smoothly 2-cyano-N'- (2-(2,4-dichlorophenoxy)acetyl)acetohydrazide (3) in an astonishing yield (98 %) as pale-yellow crystals.…”

“…Intriguingly, the extensive use of cyanoacetohydrizide derivatives dramatically represents an important class for the design and synthesis of various heterocycles by employment the electrophilic and nucleophilic sites which are present in it as reported in our previous work. [17,[19][20][21][22][23][24][25][26][27][28][29] One of the interesting reasons for design of building block containing chlorine motifs is owing to the insecticidal activity of the obtained 2,4dichlorobenzylidenecyanoacetohydrazide derivative which has remarkable potent approximately convergent with LC 50 of methoxyfenozide against cotton leaf worm (Spodoptera littoralis) in the recent our article. [24] Herein, we focused our interest in the laboratory to design and synthesize of 2-cyano-N'-(2-(2,4-dichlorophenoxy)acetyl)acetohydrazide 3.…”

Design, Synthesis and Evaluation of Thioacetamide‐Tethered Thiadiazole‐1,2,4‐Triazole Hybrids as SHP2 Inhibitors for Cancer Therapy

“…Drying overnight at 60 °C in a tray drier oven afforded the desired final compounds 16-36. (16) (18) 13 C NMR (126 MHz, DMSO-d 6 ) δ 171. 35, 166.28, 159.33, 150.27, 149.45, 130.33, 129.63, 129.22, 126.25, 125.50, 119.97, 112.46, 109.43, 56.08, 55.96, 38.86.…”

“…It should be mentioned here that 1,3,4-thiadiazole ring is well known for its anticancer and antibacterial property which arises from it being bioisosteric with pyrimidine, the principal component of thymine, cytosine and uracil nucleobases. [15][16][17] Also, many thiadiazole bearing compounds have been shown to inhibit cancerous cells like MCF-7 (breast cancer) [18] and tumorigenic enzymes like carbonic anhydrase IX (solid tumor). [19] In a nutshell, it can be stated that there are reports of many five membered heterocyclic scaffolds as SHP2 inhibitors and we envisaged evaluating the five membered heterocyclic bis-hybrid backbone connected with an activated linker.…”