Synthesis and antitumor activity of (4-hydroxyphenyl)[5-substituted alkyl/aryl)-2-thioxo-1,3,4-thiadiazol-3-yl]methanone and [(3,4-disubstituted)-1,3-thiazol-2ylidene]-4-hydroxybenzohydrazide
Abstract:To examine new drug leads with potential anticancer activity, some (4-hydroxyphenyl)[5-substituted alkyl/aryl)-2-thioxo-1,3,4-thiadiazol-3-yl]methanone (4.a-4.c) and [-(3,4-disubstituted)-1,3-thiazol-2ylidene)]-4-hydroxybenzohydrazide (6.a-6.d) were synthesized using appropriate synthetic route. The newly prepared compounds 4.a-4.c and 6.a-6.d demonstrated inhibitory effects on the growth of a wide range of cancer cell lines especially on leukemia (HL-60), non-small lung cancer (HOP-92), renal cancer (ACHN) at… Show more
“…Compound (4‐hydroxyphenyl)[5‐(2,6‐dichloro)‐2‐thioxo‐1,3,4‐thiadiazol‐3‐yl]methanone ( 42 ) showed broad spectrum of growth inhibition activity against human tumor cells and remarkable cytotoxic activity on nonsmall lung cancer (HOP 92) having log GI 50 value at ‐6.49, colon cancer (HCC‐2998) at GI 50 value −5.31 and significant cytotoxic activity on prostate cancer (PC‐3) having GI 50 value −5.48. SAR study revealed that electron withdrawing group at position C‐5 of thiadiazol was favorable for activity .…”
Section: Methodsmentioning
confidence: 99%
“…48. SAR study revealed that electron withdrawing group at position C-5 of thiadiazol was favorable for activity [37]. (47), with ID 50 two times lower (SW707, T47D) than that of cis-platin displayed the highest cytotoxicty.…”
The 1,3,4-thiadiazole nucleus is one of the most important and well-known heterocyclic nuclei, which is a common and integral feature of a variety of natural products and medicinal agents. Thiadiazole nucleus is present as a core structural component in an array of drug categories such as antimicrobial, anti-inflammatory, analgesic, antiepileptic, antiviral, antineoplastic, and antitubercular agents. The broad and potent activity of thiadiazole and their derivatives has established them as pharmacologically significant scaffolds. In this study, an attempt has been made with recent research findings on this nucleus, to review the structural modifications on different thiadiazole derivatives for various pharmacological activities.
“…Compound (4‐hydroxyphenyl)[5‐(2,6‐dichloro)‐2‐thioxo‐1,3,4‐thiadiazol‐3‐yl]methanone ( 42 ) showed broad spectrum of growth inhibition activity against human tumor cells and remarkable cytotoxic activity on nonsmall lung cancer (HOP 92) having log GI 50 value at ‐6.49, colon cancer (HCC‐2998) at GI 50 value −5.31 and significant cytotoxic activity on prostate cancer (PC‐3) having GI 50 value −5.48. SAR study revealed that electron withdrawing group at position C‐5 of thiadiazol was favorable for activity .…”
Section: Methodsmentioning
confidence: 99%
“…48. SAR study revealed that electron withdrawing group at position C-5 of thiadiazol was favorable for activity [37]. (47), with ID 50 two times lower (SW707, T47D) than that of cis-platin displayed the highest cytotoxicty.…”
The 1,3,4-thiadiazole nucleus is one of the most important and well-known heterocyclic nuclei, which is a common and integral feature of a variety of natural products and medicinal agents. Thiadiazole nucleus is present as a core structural component in an array of drug categories such as antimicrobial, anti-inflammatory, analgesic, antiepileptic, antiviral, antineoplastic, and antitubercular agents. The broad and potent activity of thiadiazole and their derivatives has established them as pharmacologically significant scaffolds. In this study, an attempt has been made with recent research findings on this nucleus, to review the structural modifications on different thiadiazole derivatives for various pharmacological activities.
“…To obtain 4-amino-3-mercapto-1,2,4-triazole intermediates 8a-i, first the acid hydrazide 6 was prepared from ethyl ester 5 by treating with hydrazine hydrate in absolute ethanol [19]. The acid hydrazide 6 was allowed to react with carbon disulphide in the presence of potassium hydroxide in methanol to give the corresponding potassium dithiocarbazinate 7.…”
Section: Designed Compoundsmentioning
confidence: 99%
“…The key intermediates 4 and 8 were synthesized according to the literature [18,19,[21][22][23]. Commercial solvents were used without any pretreatment.…”
A series of new triazole alcohol antifungals were designed by replacing one of the triazolyl moiety from fluconazole with a distinct 4-amino-3-mercapto-1,2,4-triazole motif, which is found in some antimicrobial agents. The antimicrobial susceptibility testing of target compounds demonstrated that the direct analogs of fluconazole (difluorophenethyl-triazoles) were less active against fungi, while compound 10h containing dichloro substitutions on both phenyl rings of the molecule had potent activity against yeasts including Candida albicans (four strains) and Cryptococcus neoformans (MICs = 2-8 μg/mL). Also, compound 10h was active against Candida parapsilosis, Epidermophyton floccosum, and Trichophyton mentagrophytes, while it showed no activity against Gram-positive and Gram-negative bacteria. Finally, a molecular docking study suggested that compound 10h interacts suitably with lanosterol 14α-demethylase, which is the key enzyme in ergosterol biosynthesis.
“…Thiazole ring is an important pharmacologically active heterocylic ring whose mono-, di-, three-substituted, condensed derivatives and reduced analogs (thiazoline, thiazolidine) have been widely studied in medicinal chemistry [ 1 , 2 , 3 , 4 , 5 , 6 ]. Among these molecules with common origin, thiazoline derivatives have attracted attention due to existing in many biochemical reactions in organisms [ 7 ]. Consequently, various thiazoline derivatives were reported with a broad spectrum of activity attributed to this property [ 8 , 9 ].…”
In this study, novel N′-(3-cyclohexyl/phenyl-4-(substituted phenyl)thiazole-2(3H)-ylidene)-2-[(5,6,7,8-tetrahydronaphthalen-2-yl)oxy]acetohydrazide (4a–4k) derivatives were synthesized and their anticancer potency were evaluated on human breast adenocarcinoma cell line (MCF-7), human lung carcinoma cell line (A549) and mouse embryoblast cell line (NIH/3T3) using the MTT method, DNA synthesis inhibition and flow cytometric analysis. Compound 4e bearing 4-methoxyphenyl moiety exhibited the highest antitumor efficiency against MCF-7 cell line with higher DNA synthesis inhibition and apoptotic cell percentages (ealy+late apoptotic cell). On the other hand, compounds 4f, 4g, and 4h bearing 4-bromo, 4-chloro and 4-florophenyl moieties, respectively caused excellent apoptosis levels against A549 cell line when treated with lower concentration even than cisplatin. Anticholinesterase activity of the compounds were also tested, compound 4h showed 49.92% inhibition of acetylcholinesterase (AChE).
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