title: Biological Validation of Novel Polysubstituted Pyrazole Candidates with in Vitro Anticancer Activities.
abstract: With the aim of developing novel antitumor scaffolds, a novel series of polysubstituted pyrazole derivatives linked to different nitrogenous heterocyclic ring systems at the C-4 position were synthesized through different chemical reactions and characterized by means of spectral and elemental analyses and their antiproliferative activity against 60 different human tumor cell lines was validated by the U.S. National Cancer Institute using a two stage process. The in vitro anticancer evaluation revealed that compound 9 showed increased potency toward most human tumor cell lines with GI50MG-MID = 3.59 µM, as compared to the standard drug sorafenib (GI50 MG-MID = 1.90 µM). At the same time, compounds 6a and 7 were selective against the HOP-92 cell line of non-small cell lung cancer with GI50 1.65 and 1.61 µM, respectively.
authors.affiliation: Department of Therapeutical Chemistry, Pharmaceutical and Drug Industries Division, National Research Centre, Giza 12622, Egypt. hh_fahmy@yahoo.com.
authors.forename: Hoda H
authors.initials: HH
authors.lastname: Fahmy
authors.affiliation: Department of Therapeutical Chemistry, Pharmaceutical and Drug Industries Division, National Research Centre, Giza 12622, Egypt. nagykhalifa@hotmail.com.|Pharmaceutical Chemistry Department, Drug Exploration &amp; Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. nagykhalifa@hotmail.com.
authors.forename: Nagy M
authors.initials: NM
authors.lastname: Khalifa
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754, Egypt. m.elalfy101@gmail.com.
authors.forename: Magda M F
authors.initials: MM
authors.lastname: Ismail
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754, Egypt. hendelsehrawi@hotmail.com.
authors.forename: Hend M
authors.initials: HM
authors.lastname: El-Sahrawy
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754, Egypt. emy28_s@hotmail.com.
authors.forename: Eman S
authors.initials: ES
authors.lastname: Nossier
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D066298:In Vitro Techniques; D015394:Molecular Structure; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000077157:Sorafenib; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D011720:Pyrazoles; D009536:Niacinamide; D000077157:Sorafenib
keywords: 1,3,4-polysubstituted pyrazole derivatives; anticancer agents; synthesis