Design and synthesis of quinazoline carboxylates against Gram-positive, Gram-negative, fungal pathogenic strains, and Mycobacterium tuberculosis

Abstract

Aim:A novel series of ethyl 5-(4-substituted phenyl)-3-methyl-6,7,8,9-tetrahydro-5H-thiazolo[2,3-b] quinazoline-2-carboxylate 3a-3j, were synthesized, characterized by spectral, elemental analyses and screened for their in vitro antibacterial and Mycobacterium tuberculosis (MTB) activities.Materials and Methods:The in vitro antibacterial and antifungal activities were determined by agar well-diffusion and cup-plate agar diffusion methods and the anti-tuberculosis (TB) screening for test compounds were evaluated against MTB H37Rv strain by Resazurin assay.Results:Among the derivatives tested, most of the compounds were found to have potent activity against microbial strains. The structure-activity relationship point of view, introduced group that enhance the lipophilicity as well ester, substituted aromatic ring at thiazole quinazoline nucleus showed increasing antimicrobial and anti TB activity. The high level of activity shown by the compounds with electron withdrawing groups in the para position on the benzene ring (3 g) suggests that these compounds could serve as leads for development of novel synthetic compounds with enhanced antibacterial and anti TB activities.Conclusion:These results provide a further insight into the structural requirements for targeting thiazolo quinazoline carboxylate to develop potential new agents to combat TB treatment.

New 2-Ethylthio-4-methylaminoquinazoline derivatives inhibiting two subunits of cytochrome bc1 in Mycobacterium tuberculosis

“…[4] For M. tb, antimycobacterial activity against strain H37Rv in vitro was previously reported for quinazoline 2-carboxylate derivatives, more precisely, thiazoloquinazoline carboxylates. [5] Furthermore, diaminoquinazolines (DAQ) were shown to selectively inhibit M. tb growth in a range of 1.3-6.1 μg/mL. [6] Although it was discovered that resistant mutants to DAQ harboured a mutation in rv3161c, a potential dioxygenase, and that DAQ act as a pro-drug in mycobacteria, the mode of action of these derivatives remains unknown in M. tb.…”

Synthesis, antibacterial evaluation, Raman, Crystal Structure and Hirshfeld Surface analysis of a new 3-(4-fluorophenyl)-6-methyl-2-(propylthio)quinazolin-4(3H)-one

“…The manipulation of their structures opens the way to the discovery of several drugs. It is well known that more than 90% of new drugs are made up of heterocyclics, which play a vital role as an interface between chemistry and biology [1][2][3][4][5][6][7][8][9][10].…”

“…Quinazolines have shown antibacterial and anti-inflammatory properties [3], as well as analgesic [4], anti-cancer [5], anti-tuberculosis [6], anticonvulsant [7], antioxidant [8], antihypertension [9] and anti-diabetes activities [10].…”

Synthesis and Antitumor Activity of Novel 4-Aminoquinazoline Derivatives Containing Benzothiazole

“…The epidermal growth factor receptor (EGFR) belongs to the ErbB family of receptor tyrosine kinases and plays a crucial role in cell proliferation, survival and differentiation via activation of downstream signaling pathways. [1][2] Quinazoline derivatives are important nitrogencontaining heterocycles [3] with a variety of pharmacological properties such as antimalarial, [4][5] antibacterial, [6][7] antiinflammatory, [8][9] anticonvulsant, [10][11] antihypertensive, [12] anti-diabetic, [13] cholinesterase inhibition [14][15] and antitumor. [16][17] Meanwhile, it can specifically block the auto-phosphorylation of the epidermal growth factor receptor and inhibit the epidermal growth factor receptor or its tyrosine kinase ultimately.…”