title: Synthesis and anti-Candidal activity of N-(4-aryl/cyclohexyl)-2-(pyridine-4-yl carbonyl) hydrazinecarbothioamide.
abstract: Eighteen N-(4-aryl/cyclohexyl)-2-(pyridine-4-yl carbonyl) hydrazinecarbothioamide derivatives were synthesized, evaluated against ten clinical isolates of Candida spp. and compared with itraconazole. Introduction of p-chloro (2c), p-iodo (2q), m-chloro (2l) and o-nitro (2r) substitution at phenyl ring of thiosemicarbazide enhanced the anti-Candida activity. Compound (2c) bearing p-cholorophenyl ring was found to be the most effective against Candida albicans ATCC 66027, Candida spp. 12810 (blood) and Candida spp. 178 (HVS) with MIC value of 0.09-0.78 μg/mL, whereas itraconazole exhibits the inhibitory activity with MIC value of 0.04-1.56 μg/mL against all tested strains. There is a correlation between anti-Candidal activity and p-chloro substitution at phenyl ring of thiosemicarbazide. All synthesized compounds were investigated for their potential cytotoxicity against non cancer cell line MCF-10A. The active compounds 2c, 2r and 2a were further investigated for their cytotoxic effects on three cancer cell lines; HT1080 (skin), HepG2 (liver) and A549 (lung). The active compounds showed minimal cytotoxic activity against non cancer cell line and all three cancer cell lines. Moreover, compound 2c displaying better activity against C. albicans ATCC66027 and Candida spp. [blood] compared to reference drug (itraconazole), represents a good lead for the development of newer, potent and broad spectrum anti-Candidal agents.
authors: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia. Electronic address: mashooqbhat@rediffmail.com.
authors: Mashooq Ahmad
authors: MA
authors: Bhat
authors: Department of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
authors: Abdul Arif
authors: AA
authors: Khan
authors: Department of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
authors: Shahanavaj
authors: S
authors: Khan
authors: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
authors: Mohamed A
authors: MA
authors: Al-Omar
authors: Department of Pharmacognosy, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
authors: Mohammad Khalid
authors: MK
authors: Parvez
authors: Department of Pharmacognosy, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
authors: Mohammed Salem
authors: MS
authors: Al-Dosari
authors: Stem Cell & Tissue Re-Engineering Program, Research Center, King Faisal Specialized Hospital & Research Center, MBC-03, PO Box 3354, Riyadh 11211, Saudi Arabia.
authors: Abdullah
authors: A
authors: Al-Dhfyan
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D025141:Drug Resistance, Fungal; D056945:Hep G2 Cells; D006801:Humans; D006834:Hydrazines / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D011725:Pyridines / Q000737:chemistry*; D013854:Thioamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D006834:Hydrazines; D011725:Pyridines; D013854:Thioamides; C023666:pyridine
keywords: Candida spp.; Cytotoxicity; In vitro anti-Candidal activity; Isoniazid; Thiosemicarbazide