Exploring the anticancer potential of thiadiazole derivatives of substituted thiosemicarbazones formed via copper-mediated cyclization
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2023
Authors
Vadakkedathu Palakkeezhillam, Vishnunarayanan Namboothiri
Haribabu, Jebiti

Suresh Kumar, Vaishnu

Manakkadan, Vipin

Rasin, Puthiyavalappil

Bhuvanesh, Nattamai

Echeverria, Cesar

Santibanez, Juan

Sreekanth, Anandaram

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A couple of N-(4)-morpholine/pyrrolidine-substituted thiosemicarbazones (TSCs) of fluorene-2-carboxaldehyde (FM and FP), and their corresponding thiadiazoles (TDZs) (CFM and CFP), were synthesized and characterized (elemental analysis, ultraviolet–visible [UV–Visible], Fourier transform infrared [FT-IR], nuclear magnetic resonance [NMR; 1H & 13C], high-resolution mass spectrometry [HRMS], and single-crystal X-ray diffraction [SCXRD]) for the evaluation of their anticancer potential. The TDZs were obtained unexpectedly and are possibly formed via single-step metal (copper)-mediated oxidative cyclizations of the TSCs. The synthesized compounds are fairly stable in phosphate buffer at the biological pH of 7.4. The density functional theory [DFT] studies were performed to predict the optimized structures and physicochemical properties of these compounds. The compounds were further subjected to computational and experimental biomolecular investigations in order to evaluate their anticancer ...activity in detail. CFM had the most potent activity against human breast adenocarcinoma (MCF-7) and human urinary bladder (T24) cancer cells, with IC50 values of 12.00 and 24.80 μM, respectively. In contrast, CFM had negligible cytotoxicity (IC50 = 98.70 μM) against kidney epithelial cells extracted from an African green monkey (Vero) normal cells. This outcome was preferable to that of the widely used medicine Cisplatin. Molecular docking studies were performed with the breast cancer protein “cytochrome P450 1A1” (CYP1A1) and bovine serum albumin (BSA) to predict how effectively the compounds bind to the receptor. The ADMET findings suggest that these compounds have considerable drug-likeness and oral bioavailability. These insights may open the door for additional medical research into the bioactivities of TSCs and TDZs produced from bioactive carbonyl compounds.
Keywords:
copper-mediated cyclization / cytotoxicity / thiadiazoles / thiosemicarbazones / X-ray crystallographySource:
Applied Organometallic Chemistry, 2023, 37, 8, e7174-Publisher:
- Wiley-Blackwell
Funding / projects:
- Prime Minister's Research Fellowship(PMRF), Ministry of Education,Government of India via NIT-Tiruchirappalli
- Fondo Nacional deCiencia y Tecnologia, Grant/AwardNumbers: 11170840, 3200391
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Institut za medicinska istraživanjaTY - JOUR AU - Vadakkedathu Palakkeezhillam, Vishnunarayanan Namboothiri AU - Haribabu, Jebiti AU - Suresh Kumar, Vaishnu AU - Manakkadan, Vipin AU - Rasin, Puthiyavalappil AU - Bhuvanesh, Nattamai AU - Echeverria, Cesar AU - Santibanez, Juan AU - Sreekanth, Anandaram PY - 2023 UR - http://rimi.imi.bg.ac.rs/handle/123456789/1325 AB - A couple of N-(4)-morpholine/pyrrolidine-substituted thiosemicarbazones (TSCs) of fluorene-2-carboxaldehyde (FM and FP), and their corresponding thiadiazoles (TDZs) (CFM and CFP), were synthesized and characterized (elemental analysis, ultraviolet–visible [UV–Visible], Fourier transform infrared [FT-IR], nuclear magnetic resonance [NMR; 1H & 13C], high-resolution mass spectrometry [HRMS], and single-crystal X-ray diffraction [SCXRD]) for the evaluation of their anticancer potential. The TDZs were obtained unexpectedly and are possibly formed via single-step metal (copper)-mediated oxidative cyclizations of the TSCs. The synthesized compounds are fairly stable in phosphate buffer at the biological pH of 7.4. The density functional theory [DFT] studies were performed to predict the optimized structures and physicochemical properties of these compounds. The compounds were further subjected to computational and experimental biomolecular investigations in order to evaluate their anticancer activity in detail. CFM had the most potent activity against human breast adenocarcinoma (MCF-7) and human urinary bladder (T24) cancer cells, with IC50 values of 12.00 and 24.80 μM, respectively. In contrast, CFM had negligible cytotoxicity (IC50 = 98.70 μM) against kidney epithelial cells extracted from an African green monkey (Vero) normal cells. This outcome was preferable to that of the widely used medicine Cisplatin. Molecular docking studies were performed with the breast cancer protein “cytochrome P450 1A1” (CYP1A1) and bovine serum albumin (BSA) to predict how effectively the compounds bind to the receptor. The ADMET findings suggest that these compounds have considerable drug-likeness and oral bioavailability. These insights may open the door for additional medical research into the bioactivities of TSCs and TDZs produced from bioactive carbonyl compounds. PB - Wiley-Blackwell T2 - Applied Organometallic Chemistry T2 - Applied Organometallic Chemistry T1 - Exploring the anticancer potential of thiadiazole derivatives of substituted thiosemicarbazones formed via copper-mediated cyclization IS - 8 SP - e7174 VL - 37 DO - 10.1002/aoc.7174 ER -
@article{ author = "Vadakkedathu Palakkeezhillam, Vishnunarayanan Namboothiri and Haribabu, Jebiti and Suresh Kumar, Vaishnu and Manakkadan, Vipin and Rasin, Puthiyavalappil and Bhuvanesh, Nattamai and Echeverria, Cesar and Santibanez, Juan and Sreekanth, Anandaram", year = "2023", abstract = "A couple of N-(4)-morpholine/pyrrolidine-substituted thiosemicarbazones (TSCs) of fluorene-2-carboxaldehyde (FM and FP), and their corresponding thiadiazoles (TDZs) (CFM and CFP), were synthesized and characterized (elemental analysis, ultraviolet–visible [UV–Visible], Fourier transform infrared [FT-IR], nuclear magnetic resonance [NMR; 1H & 13C], high-resolution mass spectrometry [HRMS], and single-crystal X-ray diffraction [SCXRD]) for the evaluation of their anticancer potential. The TDZs were obtained unexpectedly and are possibly formed via single-step metal (copper)-mediated oxidative cyclizations of the TSCs. The synthesized compounds are fairly stable in phosphate buffer at the biological pH of 7.4. The density functional theory [DFT] studies were performed to predict the optimized structures and physicochemical properties of these compounds. The compounds were further subjected to computational and experimental biomolecular investigations in order to evaluate their anticancer activity in detail. CFM had the most potent activity against human breast adenocarcinoma (MCF-7) and human urinary bladder (T24) cancer cells, with IC50 values of 12.00 and 24.80 μM, respectively. In contrast, CFM had negligible cytotoxicity (IC50 = 98.70 μM) against kidney epithelial cells extracted from an African green monkey (Vero) normal cells. This outcome was preferable to that of the widely used medicine Cisplatin. Molecular docking studies were performed with the breast cancer protein “cytochrome P450 1A1” (CYP1A1) and bovine serum albumin (BSA) to predict how effectively the compounds bind to the receptor. The ADMET findings suggest that these compounds have considerable drug-likeness and oral bioavailability. These insights may open the door for additional medical research into the bioactivities of TSCs and TDZs produced from bioactive carbonyl compounds.", publisher = "Wiley-Blackwell", journal = "Applied Organometallic Chemistry, Applied Organometallic Chemistry", title = "Exploring the anticancer potential of thiadiazole derivatives of substituted thiosemicarbazones formed via copper-mediated cyclization", number = "8", pages = "e7174", volume = "37", doi = "10.1002/aoc.7174" }
Vadakkedathu Palakkeezhillam, V. N., Haribabu, J., Suresh Kumar, V., Manakkadan, V., Rasin, P., Bhuvanesh, N., Echeverria, C., Santibanez, J.,& Sreekanth, A.. (2023). Exploring the anticancer potential of thiadiazole derivatives of substituted thiosemicarbazones formed via copper-mediated cyclization. in Applied Organometallic Chemistry Wiley-Blackwell., 37(8), e7174. https://doi.org/10.1002/aoc.7174
Vadakkedathu Palakkeezhillam VN, Haribabu J, Suresh Kumar V, Manakkadan V, Rasin P, Bhuvanesh N, Echeverria C, Santibanez J, Sreekanth A. Exploring the anticancer potential of thiadiazole derivatives of substituted thiosemicarbazones formed via copper-mediated cyclization. in Applied Organometallic Chemistry. 2023;37(8):e7174. doi:10.1002/aoc.7174 .
Vadakkedathu Palakkeezhillam, Vishnunarayanan Namboothiri, Haribabu, Jebiti, Suresh Kumar, Vaishnu, Manakkadan, Vipin, Rasin, Puthiyavalappil, Bhuvanesh, Nattamai, Echeverria, Cesar, Santibanez, Juan, Sreekanth, Anandaram, "Exploring the anticancer potential of thiadiazole derivatives of substituted thiosemicarbazones formed via copper-mediated cyclization" in Applied Organometallic Chemistry, 37, no. 8 (2023):e7174, https://doi.org/10.1002/aoc.7174 . .