Aminothiazole derivatives have been reported
2-Aminothiazole derivatives have been reported to contain antiviral , anti-inflammatory , and antimicrobial  activities. The in vitro anticancer studies showed that different 2-aminothiazole derivatives possess selective and potent inhibitory effect against wide-ranging human cancerous cell such as prostate, leukemia, renal, breast, CNS, lung, ovarian, colon, melanoma cell lines , , , . Some of the 2-aminothiazole derivatives have also been reported as enzymes inhibitors, such as kynurenine-3-hydroxylase or cyclin-dependent kinase .
1,2,4-Triazole is the organic heterocyclic NPPB containing two carbon atoms and three nitrogen atoms at nonadjacent position in five membered di-unsaturated ring. It is aromatic and containing molecular formula C2H3N3. This parent compound itself has been screened for antimicrobial and anticancer activity , . Over the last decade, different 1,2,4-triazole derivatives have taken attention due to their considerable antiviral, anti-inflammatory, antitumor , , , anticancer , antifungal , , analgesic  and antibacterial activities . 1,2,4-Triazole compounds also possess remarkable applications in agriculture , , .
Skin aging whether intrinsic or extrinsic is a natural process which occurs due to exposure of skin by chronic ultra violet radiation. The continuous exposure of ultra violet radiations becomes the cause of physical changes in the connective tissues and skin by the formation of reactive oxygen species and lipid peroxides . This can lead to the loss of skin elasticity which can ultimately become the cause of wrinkle formation, brown spots, skin cancer, uneven pigmentation, leathery appearance, solar elastosis, laxity and melanoma , , . The major responsible enzyme for wrinkle formation and dehydration on the skin is elastase . Elastase is responsible for delayed wound healings, increased inflammation progress and tissue permeability. Elastin is the protein widely distributed in the vertebrate tissues of human beings especially abundant in ligaments, lungs and skin, which is being hydrolyzed or cleaved by elastase enzyme belonging to the class of serine proteases . It is also the key enzyme which attacks the all major matrix protein of connective tissue .
Recently, some medicinal plant’s extracts ,  have been reported as elastase inhibiting cosmeceuticals. In addition, some synthesized compounds, such as safranal , aryl and heteroaryl oxime ester derivatives , S-substituted perhalo-2-nitrobuta-1,3-dienes , and thiazol-2-(3H)-ones  have been reported as elastase inhibitors, but still the need for the development of superior and novel inhibitors is evident. Therefore, in continuation of previous efforts to explore the enzyme inhibitory potential of related bi-heterocyclic bi-amides , the present investigation was designed to seek some novel ethylated thiazole-triazole acetamide hybrids as elastase inhibitors to devastate the problems of skin melanoma, wrinkle formation, uneven pigmentation, and solar elastosis.
Results and discussion
Conclusion A structurally unique series of bi-heterocyclic acetamides was synthesized as promising elastase inhibitor. Particularly, the compound 9h (IC50 = 0.0094 ± 0.0023 µM) bearing 2-methylphenyl ring and 9i (IC50 = 0.0887 ± 0.0195 µM) having 3-methylphenyl group possessed very excellent activities. Moreover, molecular docking results also envisaged their binding within the active region of elastase with good docking energy values. Taken together, it was concluded generally that these bi-heterocyclic acetamides might be utilized as leading medicinal scaffolds for the treatment of elastase related disorders.
Experimental Chemicals were purchased from Sigma Aldrich & Alfa Aesar (Germany) and solvents of analytical grades were supplied by local suppliers. By using open capillary tube method, melting points were taken on Griffin and George apparatus and were uncorrected. By using thin layer chromatography (with ethyl acetate and n-hexane (30:70) as mobile phase), initial purity of compounds was detected at 254 nm. Elemental analyses were performed on a Foss Heraeus CHN-O-Rapid instrument and were within ± 0.4% of the theoretical values. IR peaks were recorded on a Jasco-320-A spectrometer by using KBr pellet method. EI-MS spectra were measured on a JEOL JMS-600H instrument with data processing system. 1H NMR signals were recorded at 600 MHz and 13C NMR at 150 MHz in DMSO‑d6 using Bruker spectrometers. The abbreviations used in interpretation of 1H NMR spectra are as follows: s, singlet; d, doublet; dd, doublet of doublets; t, triplet; br.t, broad triplet; q, quartet; quin, quintet; m, multiplet; dist. distorted.