ABSTRACT
In continuation of our previous work on cancer and inflammation, 15 novel pyrazole-pyrazoline hybrids (WSPP1-15) were synthesized and fully characterized. The formation of the pyrazoline ring was confirmed by the appearance of three doublets of doublets in 1 H nuclear magnetic resonance spectra exhibiting an AMX pattern for three protons (HA , HM , and HX ) of the pyrazoline ring. All the synthesized compounds were screened for their in vitro anticancer activity against five cell lines, that is, MCF-7, A549, SiHa, COLO205, and HepG2 cells, using the MTT growth inhibition assay. 5-Fluorouracil was taken as the positive control in the study. It was observed that, among them, WSPP11 was found to be active against A549, SiHa, COLO205, and HepG2 cells, with IC50 values of 4.94, 4.54, 4.86, and 2.09 µM. All the derivatives were also evaluated for their cytotoxicity against HaCaT cells. WSPP11 was also found to be nontoxic against normal cells (cell line HaCaT), with an IC50 value of more than 50 µM. The derivatives were also evaluated for their in vitro anti-inflammatory activity by the protein (egg albumin) denaturation assay and the red blood cell membrane stabilizing assay, using diclofenac sodium and celecoxib as standard. Compounds that showed significant anticancer and anti-inflammatory activities were further studied for COX-2 inhibition. The manifestation of a higher COX-2 selectivity index of WSPP11 as compared with other derivatives and an in vitro anticancer activity against four cell lines further established that compounds that were more selective toward COX-2 also exhibited a better spectrum of activity against various cancer cell lines.
Subject(s)
Antineoplastic Agents/pharmacology , Cyclooxygenase 2 Inhibitors/pharmacology , Neoplasms/drug therapy , Pyrazoles/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cyclooxygenase 2 Inhibitors/chemical synthesis , Cyclooxygenase 2 Inhibitors/chemistry , Drug Design , Fluorouracil/pharmacology , Humans , Inhibitory Concentration 50 , Neoplasms/pathology , Pyrazoles/chemical synthesis , Pyrazoles/chemistry , Structure-Activity RelationshipABSTRACT
1,3,4-Oxadiazole, a five-membered aromatic ring can be seen in a number of synthetic molecules. The peculiar structural feature of 1,3,4-oxadiazole ring with pyridine type of nitrogen atom is beneficial for 1,3,4-oxadiazole derivatives to have effective binding with different enzymes and receptors in biological systems through numerous weak interactions, thereby eliciting an array of bioactivities. Research in the area of development of 1,3,4-oxadiazole-based derivatives has become an interesting topic for the scientists. A number of 1,3,4-oxadiazole based compounds with high therapeutic potency are being extensively used for the treatment of different ailments, contributing to enormous development value. This work provides a systematic and comprehensive review highlighting current developments of 1,3,4-oxadiazole based compounds in the entire range of medicinal chemistry such as anticancer, antifungal, antibacterial, antitubercular, anti-inflammatory, antineuropathic, antihypertensive, antihistaminic, antiparasitic, antiobesity, antiviral, and other medicinal agents. It is believed that this review will be of great help for new thoughts in the pursuit for rational designs for the development of more active and less toxic 1,3,4-oxadiazole based medicinal agents.
