Et3nh HSO4 Catalyzed Efficient Synthesis of 5-Arylidene-Rhodanine Conjugates and Their
[Et3NH][HSO4] Catalyzed Efficient Synthesis of 5-Arylidene-rhodanine Conjugates and their Antitubercular Activity
Dnyaneshwar D. Subhedar,a Mubarak H. Shaikh,a Laxman Nawale,b Amar Yeware,b Dhiman Sarkar,b Bapurao B. Shingate*a
aUGC-SAP and DST-FIST Sponsored, Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, 431 004, India
bCombichem Bioresource Center, Organic Chemistry Division, CSIR-National Chemical Laboratory, Pune 411 008
E-mail:* (B. B. Shingate)
*Corresponding author. Tel.: (91)-240-2403312; Fax: (91)-240-2403113
Scheme S1. Synthesis of 2-thioxothiazolidin-4-one and 2-(4-oxo-2-thioxothiazolidin-3-yl)acetic acid (2a-b).
Table S1. Optimization of catalyst concentrationa
Entries / Mol % / Solvent / Time (min) / Temp (°C) / Yieldb (%)1 / 5 / solvent free / 20 / 80 / 48
2 / 10 / solvent free / 20 / 80 / 69
3 / 15 / solvent free / 20 / 80 / 82
4 / 20 / solvent free / 20 / 80 / 94
5 / 25 / solvent free / 20 / 80 / 94
aReaction conditions: 1a (1 mmol), 2a (1 mmol) at 80 °C for 20 min. bIsolated yield.
Table S2. Recycling of the IL in the synthesis of (Z)-5-benzylidene-2-thioxothiazolidin-4-onea
Entry / Run / Time (min) / Yield (%)b1 / I / 20 / 94
2 / II / 20 / 94
3 / III / 20 / 92
4 / IV / 20 / 92
5 / V / 20 / 90
aReaction conditions: 1a (1 mmol), 2a (1 mmol) and 20 mol% [Et3NH][HSO4] at 80 °C. bIsolated yield.
Table S3. Antitubercular activity of compounds against avirulent strain of dormant MTB H37Ra
Comp / % Inhibition of MTB H37Ra growth in presence of compounds / Comp / % Inhibition of MTB H37Ra growth in presence of compounds30 µg/mL / 10 µg/mL / 3 µg/mL / 30 µg/mL / 10 µg/mL / 3 µg/mL
3a / 72.9 / 28.1 / 56.6 / 4a / -48.6 / -15.5 / 7.7
3b / 92.8 / 75.4 / -44.9 / 4b / -1.0 / 31.5 / 27.6
3c / 67.0 / 42.7 / 40.9 / 4c / 29.8 / 43.2 / 48.9
3d / 76.2 / 25.9 / 40.1 / 4d / 33.7 / 39.4 / 32.9
3e / 38.4 / 39.0 / 23.0 / 4e / 32.5 / 42.6 / 37.2
3f / 71.1 / 40.9 / 30.2 / 4f / 49.0 / 46.6 / 22.0
3g / 81.6 / 52.3 / 36.7 / 4g / -45.6 / -2.7 / 16.7
3h / 97.3 / 77.6 / 57.2 / 4h / -33.3 / -1.1 / 22.1
The % Inhibition in the presence of test material is calculated by following formula.% inhibition = (Average of Control-Average of Compound)/ (Average of Control-Average of Blank) X 100), where control is culture medium with cells and DMSO and blank is culture medium without cells. For all samples, each compound concentration was tested in triplicates in a single experiment.
Table S4. Antitubercular activity of compounds against avirulent strain of dormant M. Bovis BCG
Comp / % Inhibition of M. bovis BCG growth in presence of compounds / Comp / % Inhibition of M. bovis BCG growth in presence of compounds30 µg/mL / 10 µg/mL / 3 µg/mL / 30 µg/mL / 10 µg/mL / 3 µg/mL
3a / 72.3 / 70.2 / 65.0 / 4a / 22.4 / 39.2 / 17.9
3b / 93.5 / 39.5 / 104.1 / 4b / 22.4 / 23.4 / 13.1
3c / 81.1 / 46.6 / -1.0 / 4c / 32.7 / 21.2 / 21.5
3d / 34.7 / 32.5 / 22.3 / 4d / 19.9 / 28.0 / 23.6
3e / 98.9 / 84.9 / 46.1 / 4e / 13.1 / 22.7 / 21.6
3f / 71.6 / 21.6 / 37.5 / 4f / 89.2 / 63.6 / 27.9
3g / 65.9 / 43.7 / 31.3 / 4g / -10.1 / -16.0 / 0.7
3h / 94.8 / 73.3 / 29.8 / 4h / -6.5 / -11.4 / 19.7
The % Inhibition in the presence of test material is calculated by following formula.% inhibition = (Average of Control-Average of Compound)/ (Average of Control-Average of Blank) X 100), where control is culture medium with cells and DMSO and blank is culture medium without cells. For all samples, each compound concentration was tested in triplicates in a single experiment.
Table S5. Primary screening of compounds against MCF-7.
Comp / MCF-7 / Comp / MCF-730 µg/mL / 10 µg/mL / 3 µg/mL / 30 µg/mL / 10 µg/mL / 3 µg/mL
3a / 31.0 / 0.0 / 0.0 / 4a / 26.8 / 22.2 / 15.7
3b / 74.3 / 53.4 / 38.5 / 4b / 23.4 / 9.3 / 6.4
3c / 47.2 / 1.8 / 14.6 / 4c / 19.1 / 7.8 / 23.7
3d / 52.4 / -6.7 / 0.0 / 4d / 19.5 / 24.6 / 4.2
3e / 31.8 / 7.8 / 12.2 / 4e / 17.1 / 28.9 / -3.0
3f / 40.2 / 15.7 / 0.0 / 4f / 30.2 / 7.1 / 2.9
3g / 17.0 / 1.2 / 11.4 / 4g / 25.9 / 11.1 / 2.7
3h / 0.0 / 0.0 / 0.0 / 4h / 26.2 / 17.0 / 0.0
The % Inhibition in the presence of test material is calculated by following formula.% inhibition = (Average of Control-Average of Compound)/ (Average of Control-Average of Blank) X 100), where control is culture medium with cells and DMSO and blank is culture medium without cells. For all samples, each compound concentration was tested in triplicates in a single experiment.
Table S6. Primary Cytotoxic study of compounds against A549.
Comp / A549 / Comp / A54930 µg/mL / 10 µg/mL / 3 µg/mL / 30 µg/mL / 10 µg/mL / 3 µg/mL
3a / 9.9 / -22.9 / 0.0 / 4a / 0.0 / -17.9 / 0.0
3b / 32.7 / 37.4 / 41.2 / 4b / -6.7 / -16.5 / 0.0
3c / 28.1 / -5.7 / 8.0 / 4c / -9.2 / -15.1 / 0.0
3d / -8.3 / 0.0 / 0.0 / 4d / -12.0 / -22.0 / 0.0
3e / 1.5 / -20.2 / -7.1 / 4e / 2.2 / 0.2 / -3.4
3f / 0.0 / 0.0 / 0.0 / 4f / -23.4 / 0.0 / 0.0
3g / -17.9 / 0.0 / -10.9 / 4g / 0.0 / 0.0 / 0.0
3h / 0.0 / 0.0 / 0.0 / 4h / -3.1 / 0.0 / -2.7
The % Inhibition in the presence of test material is calculated by following formula.% inhibition = (Average of Control-Average of Compound)/ (Average of Control-Average of Blank) X 100), where control is culture medium with cells and DMSO and blank is culture medium without cells. For all samples, each compound concentration was tested in triplicates in a single experiment.
Table S7. Primary Cytotoxic study of compounds against HCT116
Comp / HCT116 / Comp / HCT11630 µg/mL / 10 µg/mL / 3 µg/mL / 30 µg/mL / 10 µg/mL / 3 µg/mL
3a / 30.1 / 21.9 / -5.2 / 4a / 15.5 / 7.3 / 3.2
3b / 61.2 / 49.9 / 45.0 / 4b / 19.3 / 13.1 / 12.1
3c / 53.0 / 51.2 / 17.3 / 4c / -11.8 / -15.4 / -13.5
3d / 48.0 / 0.0 / 0.0 / 4d / -7.6 / 0.0 / -9.9
3e / 4.3 / 8.5 / -12.8 / 4e / 6.1 / 6.5 / 0.2
3f / 53.7 / 45.8 / 0.1 / 4f / 13.6 / 11.2 / 11.5
3g / 31.0 / 31.7 / 14.2 / 4g / 23.5 / -19.4 / -29.3
3h / 11.5 / 8.6 / -4.4 / 4h / 23.8 / 7.9 / 4.6
The % Inhibition in the presence of test material is calculated by following formula.% inhibition = (Average of Control-Average of Compound)/ (Average of Control-Average of Blank) X 100), where control is culture medium with cells and DMSO and blank is culture medium without cells. For all samples, each compound concentration was tested in triplicates in a single experiment.
[Et3NH][HSO4]. 1H NMR, 400 MHz, DMSO-d6
[Et3NH][HSO4]. 13C NMR, 100 MHz, DMSO-d6
[Et3NH][HSO4]. FT-IR
Compound 3a. 1H NMR, 400 MHz, DMSO-d6
Compound 3a. 13C NMR, 100 MHz, DMSO-d6
Compound 3a. HRMS
Compound 3b. 1H NMR, 400 MHz, DMSO-d6
Compound 3b. 13C NMR, 100 MHz, DMSO-d6
Compound 3b. HRMS
Compound 3c. 1H NMR, 400 MHz, DMSO-d6
Compound 3c. 13C NMR, 100 MHz, DMSO-d6
Compound 3c. HRMS
Compound 3d. 1H NMR, 400 MHz, DMSO-d6
Compound 3d. 13C NMR, 100 MHz, DMSO-d6
Compound 3d. HRMS
Compound 3e. 1H NMR, 400 MHz, DMSO-d6
Compound 3e. 13C NMR, 100 MHz, DMSO-d6
Compound 3e. HRMS
Compound 3f. 1H NMR, 400 MHz, DMSO-d6
Compound 3f. 13C NMR, 100 MHz, DMSO-d6
Compound 3f. HRMS
Compound 3g. 1H NMR, 400 MHz, DMSO-d6
Compound 3g. 13C NMR, 100 MHz, DMSO-d6
Compound 3g. HRMS
Compound 3h. 1H NMR, 400 MHz, DMSO-d6
Compound 3h. 13C NMR, 100 MHz, DMSO-d6
Compound 3h. HRMS
Compound 4a. 1H NMR, 400 MHz, DMSO-d6
Compound 4a. 13C NMR, 100 MHz, DMSO-d6
Compound 4a. HRMS
Compound 4b. 1H NMR, 400 MHz, DMSO-d6
Compound 4b. 13C NMR, 100 MHz, DMSO-d6
Compound 4b. HRMS
Compound 4c. 1H NMR, 400 MHz, DMSO-d6
Compound 4c. 13C NMR, 100 MHz, DMSO-d6
Compound 4c. HRMS
Compound 4d. 1H NMR, 400 MHz, DMSO-d6
Compound 4d. 13C NMR, 100 MHz, DMSO-d6
Compound 4d. HRMS
Compound 4e. 1H NMR, 400 MHz, DMSO-d6
Compound 4e. 13C NMR, 100 MHz, DMSO-d6
Compound 4e. HRMS
Compound 4f. 1H NMR, 400 MHz, DMSO-d6
Compound 4f. 13C NMR, 100 MHz, DMSO-d6
Compound 4f. HRMS
Compound 4g. 1H NMR, 400 MHz, DMSO-d6
Compound 4g. 13C NMR, 100 MHz, DMSO-d6
Compound 4g. HRMS
Compound 4h. 1H NMR, 400 MHz, DMSO-d6
Compound 4h. 13C NMR, 100 MHz, DMSO-d6
Compound 4h. HRMS