جستجوی مقالات مرتبط با کلیدواژه « thiazole » در نشریات گروه « پزشکی »

Alzheimer's disease (AD) is a common neurodegenerative disease and the fifth leading cause of death among the elderly. The development of drugs for AD treatment is based on inhibiting cholinesterase (ChE) activity and inhibiting amyloid-beta peptide and tau protein aggregations. Many in vitro findings have demonstrated that thiazole- and thiazolidine-based compounds have a good inhibitory effect on ChE and other elements involved in the AD pathogenicity cascade.

Experimental approach: 

In the present review, we collected available documents to verify whether these synthetic compounds can be a step forward in developing new medications for AD. A systematic literature search was performed in major electronic databases in April 2021. Twenty-eight relevant in vitro and in vivo studies were found and used for data extraction.

Findings demonstrated that thiazole- and thiazolidine-based compounds could ameliorate AD's pathologic condition by affecting various targets, including inhibition of ChE activity, amyloid-beta, and tau aggregation in addition to cyclin-dependent kinase 5/p25, beta-secretase-1, cyclooxygenase, and glycogen synthase kinase-3β.

Conclusion and implications: 

Due to multitarget effects at micromolar concentration, this review demonstrated that these synthetic compounds could be considered promising candidates for developing anti-Alzheimer drugs.

Pyridopyrimidine and its derivatives have a variety of chemical and biological significances. Thiazole-containing compounds have also been reported to have a wide range of biological activities. Due to the valuable cytotoxic effects of both thiazole and pyridopyrimidinone derivatives, a series of pyridopyrimidinone-thiazole hybrids were synthesized in the present study.

Experimental approach:

Briefly, different acyl chlorides were reacted with 2-amino nicotinic acid followed by anhydride acetic to give the corresponding pyridobenzoxazinones. The aminothiazole derivative G was also prepared via</em> a multistep procedure and incorporated into the benzoxazinones to furnish the target pyridopyrimidinone, K1-K5. Furthermore, the cytotoxic activity of the final compounds was determined against MCF-7 and HeLa cell lines using MTT assay.

The results indicated that aromatic substitution on C2 of pyridopyrimidine nucleus was in favor of cytotoxic activity on both cell lines, of which, compound K5 bearing a chlorophenyl group showed the highest cytotoxicity.

Conclusion and implications:

 The results of the present study are valuable in terms of synthesis of hybrid molecules and also cytotoxic evaluations which can be useful for future investigations about the design of novel pyridopyrimidinone-thiazole hybrids possessing better cytotoxic activities.

Considering the diversified pharmacological importance of thiazole and triazole heterocyclic moieties, a unique series of S-aralkylated bi-heterocyclic hybrids, 7a-l, was synthesized in a convergent manner. The structures of newly synthesized compounds were characterized by 1H-NMR, 13C-NMR, IR, and EI-MS spectral studies. The structure-activity relationship of these compounds was envisaged by analyzing their inhibitory effects against tyrosinase, whereby all these molecules exhibited potent inhibitory potentials relative to the standard used. The Kinetics mechanism was ascertained by Lineweaver-Burk plots, which revealed that 7g inhibited tyrosinase non-competitively by forming an enzyme-inhibitor complex. The inhibition constants Ki calculated from Dixon plots for this compound was 0.0057µM. These bi-heterocyclic molecules also disclosed good binding energy values (kcal/mol) when assessed computationally. So, these molecules can be considered promising medicinal scaffolds for the treatment of skin disorders.

Cancer is the second important reason for death worldwide. In spite of advances in cancer treatment, however, survival of patients stays weak. Therefore, there is a critical need for advancement of new anticancer drugs. Regarding the hopeful biological activity of phthalimide derivatives, in this study, synthesis, cytotoxicity, and pro‐apoptosis activity of eleven derivatives of thiazole bearing phthalimide structure were evaluated.

First, target derivatives were synthesized. All synthesized compounds were characterized by spectroscopic methods. Cytotoxicity and pro‐apoptosis activity of the synthesized compounds were evaluated in MDA-MB-468, PC-12, and MCF-7 cancer cell lines by MTT assay, caspase-3 activity, and TUNEL assay. Finally, expression of BAX, BCL-2, and FAS (as markers of apoptosis) was assessed by the RT-PCR procedure.

Among the eleven compounds, 5b (IC50 = 0.2±0.01 µM) was found to be the most potent derivative against MCF-7 cells. Also, Compound 5k and 5g showed strong cytotoxic activity against MDA-MB-468 and PC-12 cells with IC50 value of 0.6±0.04 µM and 0.43±0.06 µM, respectively.  DNA fragmentation and activity of caspase-3 data suggest that cytotoxic activity of the compounds on cancer cells might be related to apoptosis. Also, RT-PCR of apoptosis markers indicated that these compounds induce apoptosis through the intrinsic pathway.

Our findings suggest that para chloro derivative (5c) may be a promising agent for treatment of cancer cells by the targeted intrinsic pathway of apoptosis and could be used as a drug candidate for in vivo assessment in the treatment of cancer.