Anticancer activity
Anti-cancer activity of imine derivatives (3a-m) were evaluated by MTT assay (Table 1-3) using glioblastoma cell line (U87). This cell line was selected as compounds showed promising activity against different causative enzymes of neurodegenerative diseases 24. Among all compound 3g showed potent anti-cancer activity against U87 cell line with IC50 value of 8.83 ± 0.23 µM. Moreover, compounds 3e, 3f, 3h and 3i also showed good to moderate anticancer activities having IC50 values of 17.73 ± 0.05 µM, 21.38 ± 0.02 µM, 12.37 ± 0.09 µM and 19.68 ± 0.06 µM respectively. Compound 3m among thiazole was the most potent compound with IC50 value of 8.86 ± 0.15 µM. Other analogues 3k and 3l also showed good to moderate anticancer activity with IC50 values of 13.68 ± 0.11 µM and 20 ± 0.22 µM respectively. Moreover, oxazole containing compound 3j also showed good activity with IC50 value of 13.17 ± 0.06 µM.
The SAR of semicarbazones and thiosemicarbazone indicated that compound 3g containing meta nitro and para methoxy groups against semicarbazide moiety showed potent inhibitory potential with IC50 value of 8.83 ± 0.23 µM changing methoxy group with hydroxyl in 3f drastically decrease the activity with IC50 value of 21.38 ± 0.02 µM. Changing nitro or methoxy group with halogens in 3e and 3h also decreases the activity with IC50 values of 17.73 ± 0.05 µM and 12.37 ± 0.09 µM correspondingly.
Among thiazoles 3m possessing nitro at meta position against thiazole moiety was most potent thiazole with IC50 value of 8.86 ± 0.15 µM. Changing nitro with halogens in 3k and 3l decreases the activity with IC50 values of 13.68 ± 0.11 µM and 20 ± 0.22 µM respectively. Compound 3j containing oxazole moiety with hydroxy groups at meta and para positions showed good activity with IC50 value of 13.17 ± 0.06 µM.
To evaluate the cytotoxic effect of synthesized derivatives on normal human cells, MTT assay was carried out in contrast to HEK-293 (Normal human embryonic kidney Cell Line). Semicarbazones and thiosemicarbazones were found non-cytotoxic with moderate anti-carcinoma activity except 3g and 3h. Though thiazole derivatives 3k and 3m were found cytotoxic, other derivatives did not show cytotoxicity against HEK-293.
Table 1: Cytotoxicity and anti-cancer assay results of synthesized semicarbazones and thiosemicarbazone
Table 2: Cytotoxicity and anti-cancer assay results of synthesized oxazole and thiazole derivatives
Anti-bacterial Activity
Anti-bacterial agents are of ultimate developments in modern medicine responsible to inhibit the growth of bacteria ultimately results in damaging them. Ideally these focus on bacteria devoid of affecting mammalian cells 25. Due to increasing bacterial resistance now a days the development of new anti-bacterial agents is of great significance.
The anti-bacterial potential of semicarbazone, thiosemicarbazone, oxazole and thiazole derivatives (3a-m) was evaluated using Agar well diffusion method against five Gram-positive bacterial strains including Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Corynebacterium diphtheriae, Klebsiella pneumoniae and five Gram-negative bacterial strains including Salmonella Typhi, Eschericia coli, Enterobacter aerogenes, Pseudomonas aeruginosa and Proteus mirabilis. Most of the synthesized derivatives showed almost negligible anti-bacterial activity. Results are illustrated in table 3.
Among semicarbazones only 3c showed slight anti-bacterial action only against gram negative strain i.e., Salmonella Typhi and gram-positive strain Cornybacterium diphthereae with zone of inhibition of 8mm for both the strains at the concentration of 200 µg/ml. Compound 3d having thio-semicarbazide moiety showed mild anti-bacterial potential against two gram positive strains including Staphylococcus aureus, Corynebacterium diphtheriae and a gram negative strain i.e., Proteus mirabilis with zone of inhibition of 10mm, 18mm and 10 mm respectively. Moreover, among oxazole and thiazoles none of the synthesized compound displayed antibacterial activity.
Table 3: Antibacterial activity results
Bacterial Strains
|
Zone of Inhibition (mm) at 200 µg/ml
|
3a
|
3b
|
3c
|
3d
|
3e
|
3f
|
3g
|
3g
|
3h
|
3i
|
3j
|
3k
|
3l
|
3m
|
Salmonella Typhi
|
-
|
-
|
8
|
-
|
-
|
-
|
-
|
-
|
-
|
1
|
-
|
2
|
-
|
-
|
Streptococcus Faecalis
|
-
|
-
|
-
|
2
|
-
|
-
|
-
|
-
|
-
|
4
|
-
|
-
|
2
|
-
|
Staphylococcus aureus
|
-
|
-
|
1
|
10
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
2
|
-
|
Staphylococcus epidermidis
|
-
|
-
|
0
|
4
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
Cornybacterium diphthereae
|
-
|
-
|
8
|
18
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
Eschericia coli
|
-
|
-
|
2
|
2
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
Proteus mirabilis
|
-
|
-
|
2
|
10
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
2
|
-
|
Enterobacter aerogenes
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
Pseudomonas aerogenosa
|
-
|
-
|
1
|
1
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
1
|
-
|
Klebsiella pneumonaea
|
-
|
-
|
-
|
2
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|