Synthesis, Molecular Modeling, and Biological Evaluation of Novel Chiral Thiosemicarbazone Derivatives as Potent Anticancer Agents

Abstract

A series of new chiral thiosemicarbazones derived from homochiral amines in both enantiomeric forms were synthesized and evaluated for their in vitro antiproliferative activity against A549 (human alveolar adenocarcinoma), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma), and HGC-27 (human stomach carcinoma) cell lines. Some of compounds showed inhibitory activities on the growth of cancer cell lines. Especially, compound exhibited the most potent activity (IC50 4.6 μM) against HGC-27 as compared with the reference compound, sindaxel (IC50 10.3 μM), and could be used as a lead compound to search new chiral thiosemicarbazone derivatives as antiproliferative agents.

Synthesis of Novel Chiral Sulfonamide‐Bearing 1,2,4‐Triazole‐3‐thione Analogs Derived fromD‐andL‐Phenylalanine Esters as Potential Anti‐Influenza Agents

“…The FT-IR spectra were measured with a Perkin Elmer (Boston, MA) 1620 model FT-IR Spectrophotometer in the region 4000-400 cm À1 with universal ATR sampling accessory. 1 H and 13 C NMR spectra were recorded in DMSO-d 6 solutions on a Bruker (Billerica, MA) AVANC-DPX-400 MHz spectrometer using tetramethylsilane (TMS) as the internal reference at 400 MHz and 100 MHz, respectively. The chemical shifts are denoted as δ values (ppm) and the splitting of the NMR is described as s (singlet), brs (broad singlet), d (doublet), dd (double doublet), t (triplet), q (quartet), p (pentet), or m (multiplet).…”

“…The chemical structures of the all compounds were elucidated by the combination of UV-Vis, IR, 1 HNMR, 13 C NMR, 2D NMR (HETCOR), MS spectral data, and elemental analysis. The IR spectra of new homochiral hydrazides (2a-2b) showed two characteristic stretching bands around 3274 cm À1 and 3322 cm À1 due to amine NH 2 /amide NH and a strong stretching band at 1653 cm À1 attributed to amide carbonyl ν(C = O).…”

“…One of the techniques used to synthesize enantiopure compounds is to start with commercially available chiral building blocks (chiral pool). For this purpose, α‐aminoacids and their derivatives that have functionalities and high enantiomeric purities that allow them to be converted into the target products can be used …”

“…For this purpose, α-aminoacids and their derivatives that have functionalities and high enantiomeric purities that allow them to be converted into the target products can be used. [13][14][15] On the other hand, recently, 1,2,4-triazole scaffolds have attracted considerable attention because of their promising biological activities such as antiviral, antifungal, antibacterial, anti-inflammatory, antidepressant, anticonvulsant, antihypertensive, analgesic, antioxidant, and anticancer. [16][17][18][19][20][21][22][23][24] The 1,2,4-triazole ring system can be used as a bioisostere of the amide group for the design of receptor ligands with enhanced pharmacokinetic properties in drug candidates.…”

“…: 3163 (N-H), 1595 (C = N), 1309 (SO 2 , asym), 1220 (C = S), 1157 (SO 2 , sym); EI-MS (m/z (%)): 480.7 (20.5) [M-H]¯, 323.7 (51.3), 291.7 (2.1), 276.7 (3.3), 162.9 (2.8), 155.9 (100), 147.9 (5.7), 92.0 (53.3), 79.9 (10.9), 79.0 (17.9), 62.0 (5.3), 58.0 (39.1); 1 H NMR (400 MHz, DMSO-d 6 ): δ 2.55 (s, 3H, SCH 3 ), 2.87 (dd, 1H, J 1 = J 2 = 7.6 Hz,-CH 2 -, H b ),3.03 (dd, 1H, J 1 = 7.2 Hz, J 2 = 7.6 Hz,-CH 2 -, H a ),3.95 (t, 1H, ÀCH-), 6.80 (dd, 2H, J 1 = 6.8 Hz, J 2 = 7.6 Hz, H meta , C ring), 7.16-7.20 (m, 4H, H ortho and H meta , A ring), 7.30 (brs, 2H, H meta , B ring), 7.42-7.48 (m, 5H, H para , A ring, H ortho , B ring and H ortho , C ring), 7.58 (t, 1H, H para , B ring),8.84 (brs, 1H, ÀNHSO 2 -),13.89 (brs, 1H, triazole-NH-);13 C NMR (100 MHz, DMSO-d 6 ): δ 14.77 (ÀSCH 3 ), 38.72 (ÀCH 2 -), 51.11 (ÀCH-), 126.31 (C ortho , C ring), 126.67 (C para , A ring), 127.49 (C ortho , B ring), 128.97 (C meta , A ring and C meta , C ring), 129.44 (C ortho , A ring and C meta , B ring), 133.07 (C para , B ring), 136.31 (C ipso , A ring and C ipso -N, C ring), 140.26 (C ipso , B ring), 141.09 (C ipso -SCH 3 , C ring), 152.22 (C = N, triazole),167.79 (C = S, triazole); Anal. Calcd.…”