Prospects for Prostate Cancer Chemotherapy: Cytotoxic Evaluation and Mechanistic Insights of Quinolinequinones with ADME/PK Profile
Abstract
:1. Introduction
2. Materials and Methods
2.1. Biological Evaluation
2.1.1. In Vitro Single-Dose Anticancer Screening by NCI
2.1.2. In Vitro Five-Dose Anticancer Screening by NCI
2.1.3. MTT Assay
2.1.4. Colony Formation Assay
2.1.5. Scratch Assay
2.1.6. Apoptosis Necrosis Analysis
2.1.7. Cell Cycle Assay
2.1.8. Oxidative Stress
2.1.9. Statistical Analysis
2.2. ADME and PK Profiling
2.2.1. In Vitro Metabolic Stability Study
2.2.2. In Vivo Bioavailability Study of AQQ1 and AQQ2 in Male Sprague-Dawley Rats
2.2.3. Bioanalytical Method (LC/MS/MS) for AQQ1 and AQQ2
2.3. Molecular Docking and Molecular Dynamics
3. Results and Discussion
3.1. Biological Evaluation
3.1.1. Preliminary Anticancer Screening
3.1.2. In Vitro Full Panel Five-Dose 60-Cell Lines Assay
3.1.3. Cytotoxicity Study of AQQ1 and AQQ2 with MTT Assay
3.2. Pharmacokinetic Profiling
3.2.1. In Vitro ADME Studies
3.2.2. In Vivo Pharmacokinetic Studies
3.3. In Silico Molecular Interaction Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Cancer Cell Lines | AQQ1 | AQQ2 | AQQ3 | AQQ4 | AQQ5 | |
---|---|---|---|---|---|---|
Leukemia | ||||||
GP | CCRF-CEM | −4.94 | −6.33 | 0.63 | 15.29 | 2.72 |
HL-60(TB) | −48.05 | −36.75 | −46.39 | 9.95 | −13.44 | |
K-562 | −21.12 | 1.26 | −4.17 | 7.18 | 4.73 | |
MOLT-4 | −39.00 | −24.89 | −46.73 | 69.83 | 8.29 | |
RPMI-8226 | −30.44 | −35.12 | −19.35 | 47.33 | −39.66 | |
SR | −27.92 | −12.75 | −27.42 | 0.92 | −3.19 | |
Non-Small Cell Lung Cancer | ||||||
GP | A549/ATCC | 101.36 | 59.11 | 46.18 | 107.06 | 42.41 |
EKVX | 28.52 | −2.24 | −97.48 | 50.81 | 74.66 | |
HOP-62 | 74.12 | 84.25 | 72.15 | 110.03 | 0.85 | |
HOP-92 | −83.81 | −89.25 | −86.99 | 112.07 | −12.23 | |
NCI-H226 | 29.65 | 17.62 | −52.55 | 97.11 | 68.59 | |
NCI-H23 | −8.37 | −67.81 | −61.00 | 59.03 | −55.61 | |
NCI-H322M | 71.14 | 28.84 | 32.37 | 99.05 | 89.75 | |
NCI-H460 | 70.83 | 12.07 | 13.41 | 100.46 | 2.02 | |
NCI-H522 | −48.50 | −43.48 | −61.57 | 78.84 | −80.61 | |
Colon Cancer | ||||||
GP | COLO 205 | 111.34 | 99.24 | 98.22 | 107.70 | −80.52 |
HCC-2998 | 58.90 | 20.35 | −55.70 | 103.69 | 14.44 | |
HCT-116 | −80.64 | −79.44 | −83.64 | 55.84 | −97.84 | |
HCT-15 | −47.03 | −76.56 | −83.19 | 82.29 | −66.21 | |
HT29 | 75.04 | 19.96 | 15.90 | 109.56 | 24.91 | |
KM12 | 69.40 | 60.77 | 57.40 | 98.23 | 39.30 | |
SW-620 | −63.13 | −66.65 | −55.33 | 72.23 | −90.16 | |
CNS Cancer | ||||||
GP | SF-268 | 47.42 | 32.75 | 32.33 | 84.69 | 37.00 |
SF-295 | 96.61 | 90.72 | 51.05 | 103.62 | 51.57 | |
SF-539 | 1.78 | −37.33 | −58.82 | 103.46 | −30.92 | |
SNB-19 | 38.92 | 46.47 | 44.68 | 94.62 | 30.42 | |
SNB-75 | 105.38 | 101.38 | 96.54 | 110.92 | −4.09 | |
U251 | 62.79 | 37.89 | 15.60 | 105.80 | 36.76 | |
Melanoma | ||||||
GP | LOX IMVI | −72.99 | −82.20 | −76.37 | −3.09 | −82.62 |
MALME-3M | −55.92 | −71.39 | −90.58 | 94.54 | −89.37 | |
M14 | ND a | ND a | ND a | ND a | −95.99 | |
MDA-MB-435 | −85.96 | −85.72 | −83.74 | −67.16 | −87.43 | |
SK-MEL-2 | 78.82 | −15.72 | −49.77 | 100.13 | 5.03 | |
SK-MEL-28 | 14.13 | 14.55 | 8.93 | 101.65 | −73.06 | |
SK-MEL-5 | −93.34 | −97.76 | −98.64 | 86.57 | −74.93 | |
UACC-257 | −82.67 | −88.33 | −89.19 | 91.03 | −92.05 | |
UACC-62 | −45.84 | −29.14 | −43.31 | 71.83 | −43.56 | |
Ovarian Cancer | ||||||
GP | IGROV1 | −83.51 | −57.52 | −82.43 | 19.63 | −23.13 |
OVCAR-3 | CN b | CN b | CN b | 13.16 | CN b | |
OVCAR-4 | −98.22 | −91.97 | −97.52 | 71.38 | −93.28 | |
OVCAR-5 | 78.91 | 40.78 | 54.83 | 104.66 | 22.00 | |
OVCAR-8 | 9.87 | 0.93 | 1.03 | 92.63 | −0.82 | |
NCI/ADR-RES | 7.08 | −9.58 | −15.63 | 94.66 | −1.26 | |
SK-OV-3 | 88.34 | 85.34 | 79.78 | 91.82 | 93.82 | |
Renal Cancer | ||||||
GP | 786-0 | 9.17 | −88.18 | 8.39 | 98.99 | −59.47 |
A498 | 71.81 | 78.84 | 100.96 | 82.55 | 71.10 | |
ACHN | −99.93 | −99.15 | −98.42 | 95.00 | −99.62 | |
CAKI-1 | ND a | ND a | ND a | ND a | −96.53 | |
RXF 393 | ND a | ND a | ND a | ND a | −97.24 | |
SN12C | −49.46 | −50.97 | −57.33 | 90.46 | −63.27 | |
TK-10 | 147.78 | 124.08 | 121.08 | 148.82 | −50.07 | |
UO-31 | −65.68 | −92.96 | −65.05 | 100.30 | −94.65 | |
Prostate Cancer | ||||||
GP | PC-3 | 27.39 | 4.34 | 10.40 | 70.56 | 27.99 |
DU-145 | −57.26 | −85.02 | −92.73 | 93.00 | −92.99 | |
Breast Cancer | ||||||
GP | MCF7 | −60.38 | −59.68 | −66.97 | 59.00 | −51.73 |
MDA-MB-231/ATCC | −57.30 | −63.63 | −71.74 | 72.96 | −28.56 | |
HS 578T | 72.15 | 1.05 | 48.97 | 118.57 | −32.78 | |
BT-549 | 83.54 | 44.40 | 46.48 | 126.22 | 24.11 | |
T-47D | −44.73 | −40.00 | −43.85 | 14.93 | −56.01 | |
MDA-MB-468 | −79.74 | −90.72 | −95.15 | 58.11 | −78.49 |
Molecule | AQQ1 (NCI: D-829432/1) | AQQ2 (NCI: D-829433/1) | AQQ3 (NCI: D-829431/1) | AQQ5 (NCI: D-830803/1) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Panel/Cell Line | GI50 | TGI | LC50 | GI50 | TGI | LC50 | GI50 | TGI | LC50 | GI50 | TGI | LC50 |
Leukemia | ||||||||||||
CCRF-CEM | 1.94 | 8.21 | >100 | 1.41 | >100 | >100 | 2.11 | >100 | >100 | 2.23 | ND a | >100 |
HL-60(TB) | 1.37 | 3.52 | 9.03 | 1.03 | 2.92 | 8.29 | 1.47 | 4.18 | >100 | 1.38 | 4.65 | >100 |
K-562 | 0.290 | 2.94 | >100 | 0.341 | ND a | >100 | 1.17 | >100 | >100 | 0.381 | >100 | >100 |
MOLT-4 | 2.27 | 8.60 | >100 | 2.03 | 8.09 | >100 | 2.49 | >100 | >100 | 1.50 | 7.00 | >100 |
RPMI-8226 | 1.57 | 4.61 | >100 | 1.20 | 4.71 | >100 | 1.67 | 5.33 | >100 | 1.79 | 5.19 | >100 |
SR | 0.794 | 4.25 | >100 | 0.543 | 4.14 | >100 | 1.09 | >100 | >100 | 0.350 | 2.43 | >100 |
Non-Small Cell Lung Cancer | ||||||||||||
A549/ATCC | 2.44 | 6.24 | 45.2 | 2.06 | 4.64 | 12.9 | 2.09 | 4.64 | 17.5 | 2.83 | 8.97 | 38.8 |
EKVX | 1.61 | 3.05 | 5.78 | 1.56 | 2.98 | 5.70 | 1.61 | 3.12 | 6.05 | 1.60 | 3.12 | 6.08 |
HOP-62 | 2.41 | 6.98 | 37.5 | 2.27 | 6.74 | 28.8 | 1.74 | 3.23 | 6.01 | 4.26 | 14.1 | 37.7 |
HOP-92 | 1.85 | 3.30 | 5.91 | 1.80 | 3.33 | 6.13 | 2.01 | 3.51 | 6.12 | 1.73 | 3.17 | 5.83 |
NCI-H226 | 1.93 | 4.52 | 14.1 | 1.78 | 4.24 | 16.2 | 1.84 | 4.52 | >100 | 2.82 | 8.35 | 46.1 |
NCI-H23 | 1.47 | 3.30 | 7.45 | 1.44 | 3.55 | 8.71 | 1.35 | 2.85 | 6.03 | 1.53 | 3.15 | 6.49 |
NCI-H322M | 2.50 | 7.69 | 27.6 | 2.22 | 7.91 | 29.7 | 1.68 | 3.74 | 8.29 | 3.42 | 12.8 | 35.8 |
NCI-H460 | 3.22 | 12 | 52.7 | 3.02 | 11.4 | 45.4 | 3.08 | 10.4 | 49.7 | 2.68 | 8.07 | 82.6 |
NCI-H522 | 1.81 | 3.36 | 6.24 | 1.74 | 3.28 | 6.18 | 1.75 | 3.22 | 5.94 | 1.56 | 3.06 | 6.02 |
Colon Cancer | ||||||||||||
COLO 205 | 1.78 | 3.87 | ND a | 1.73 | 3.66 | 7.74 | 1.86 | 3.64 | 7.12 | 1.68 | 3.08 | 5.63 |
HCC-2998 | 1.87 | 3.46 | 6.42 | 1.94 | 3.52 | 6.39 | 1.76 | 3.25 | 6.00 | 1.81 | 3.26 | 5.88 |
HCT-116 | 1.53 | 4.16 | 44.3 | 1.05 | 2.31 | 5.05 | 1.32 | 2.79 | 5.92 | 1.53 | 2.88 | 5.45 |
HCT-15 | 1.33 | 3.02 | 6.83 | 1.13 | 2.55 | 5.76 | 1.30 | 2.94 | 6.66 | 1.54 | 3.92 | ND a |
HT29 | 2.13 | 4.49 | 9.46 | 3.40 | 15.2 | 99.5 | 2.87 | 7.08 | 62.5 | 1.87 | 3.48 | 6.48 |
KM12 | 1.49 | 3.08 | 6.40 | 1.41 | 2.89 | 5.92 | 1.44 | 3.07 | 6.51 | 13.0 | 26.6 | 54.7 |
SW-620 | 1.84 | 3.73 | 7.56 | 1.60 | 3.21 | 6.41 | 1.83 | 3.51 | 6.73 | 1.76 | 3.47 | 6.85 |
CNS Cancer | ||||||||||||
SF-268 | 1.53 | 3.05 | 6.06 | 1.47 | 2.94 | 5.87 | 1.55 | 3.09 | 6.14 | 3.25 | 14.4 | 72.7 |
SF-295 | 1.85 | 3.42 | 6.32 | 2.03 | 4.20 | 8.70 | 1.86 | 3.43 | 6.30 | 1.99 | 5.41 | 20.8 |
SF-539 | 1.68 | 3.13 | 5.81 | 1.67 | 3.09 | 5.71 | 1.68 | 3.13 | 5.84 | 1.79 | 3.22 | 5.78 |
SNB-19 | 1.81 | 3.72 | 7.64 | 1.80 | 3.97 | 8.73 | 1.68 | 3.16 | 5.94 | 5.82 | 18.8 | 44.2 |
SNB-75 | 1.50 | 2.84 | 5.39 | 1.63 | 3.43 | 7.21 | 1.46 | 2.79 | 5.33 | 1.94 | 5.37 | 23.2 |
U251 | 1.85 | 3.73 | 7.53 | 1.70 | 3.27 | 6.28 | 1.80 | 3.54 | 6.94 | 1.92 | 4.44 | 10.8 |
Melanoma | ||||||||||||
LOX IMVI | 0.952 | 2.36 | 5.70 | 0.839 | 2.22 | 5.33 | 1.06 | 2.33 | 5.14 | 1.10 | 2.32 | 4.88 |
MALME-3M | 1.71 | 3.19 | 5.95 | 1.36 | 2.77 | 5.64 | 1.65 | 3.16 | 6.02 | 1.76 | 3.28 | 6.11 |
M14 | 1.82 | 3.81 | 7.96 | 1.46 | 2.83 | 5.50 | 1.68 | 3.23 | 6.21 | 1.69 | 3.09 | 5.66 |
MDA-MB-435 | 1.70 | 3.11 | 5.67 | 0.266 | 0.671 | 2.45 | 0.442 | 1.53 | 3.99 | 1.72 | 3.57 | 7.39 |
SK-MEL-2 | 1.81 | 3.34 | 6.19 | 1.44 | 2.86 | 5.69 | 1.63 | 3.03 | 5.64 | 1.59 | 3.10 | 6.03 |
SK-MEL-28 | 1.85 | 3.34 | 6.02 | 1.71 | 3.14 | 5.79 | 1.73 | 3.14 | 5.70 | 1.79 | 3.23 | 5.85 |
SK-MEL-5 | 1.75 | 3.17 | 5.74 | 1.74 | 3.13 | 5.65 | 1.72 | 3.11 | 5.62 | 1.62 | 2.97 | 5.47 |
UACC-257 | 1.57 | 3.09 | 6.11 | 1.28 | 2.61 | 5.34 | 1.39 | 2.78 | 5.58 | 1.51 | 2.85 | 5.37 |
UACC-62 | 1.82 | 3.37 | 6.25 | 1.80 | 3.36 | 6.28 | 1.81 | 3.29 | 5.97 | 1.77 | 3.42 | 6.60 |
Ovarian Cancer | ||||||||||||
IGROV1 | 1.46 | 2.92 | 5.86 | 1.37 | 2.82 | 5.84 | 1.36 | 2.76 | 5.61 | 1.73 | 3.55 | 7.26 |
OVCAR-3 | 1.12 | 2.40 | 5.15 | 0.759 | 2.03 | 4.54 | 0.962 | 2.19 | 4.87 | ND a | ND a | ND a |
OVCAR-4 | 1.21 | 2.49 | 5.11 | 1.00 | 2.22 | 4.91 | 1.13 | 2.37 | 4.97 | 1.40 | 2.82 | 5.66 |
OVCAR-5 | 1.86 | 3.42 | 6.29 | 1.84 | 3.33 | 6.03 | 1.92 | 3.46 | 6.25 | 2.38 | 5.79 | 23.7 |
OVCAR-8 | 1.61 | 3.25 | 6.59 | 1.49 | 2.92 | 5.70 | 1.57 | 3.01 | 5.77 | 1.64 | 3.28 | 6.56 |
NCI/ADR-RES | 2.03 | 5.16 | 34.6 | 1.89 | 5.09 | >100 | 1.70 | 4.11 | 9.93 | 1.81 | 4.47 | 21.7 |
SK-OV-3 | 12.6 | 27.5 | 59.8 | 13.5 | 27.1 | 54.2 | 11.0 | 30.1 | 82.3 | 12.6 | 25.1 | 50.1 |
Renal Cancer | ||||||||||||
786-0 | 1.91 | 3.61 | 6.82 | 1.80 | 3.25 | 5.86 | 1.72 | 3.19 | 5.89 | 1.52 | 2.88 | 5.44 |
A498 | 1.90 | 4.60 | 13.1 | 2.65 | 10.8 | 34.8 | 1.56 | 5.52 | 24.4 | 2.35 | 11.4 | 33.8 |
ACHN | 1.47 | 2.80 | 5.34 | 1.35 | 2.69 | 5.35 | 1.57 | 2.92 | 5.45 | 1.67 | 3.04 | 5.51 |
CAKI-1 | 1.50 | 2.87 | 5.47 | 1.45 | 2.84 | 5.57 | 1.60 | 2.97 | 5.51 | 1.76 | 3.15 | 5.65 |
RXF 393 | 1.42 | 2.76 | 5.36 | 1.44 | 2.78 | 5.39 | 1.57 | 2.96 | 5.61 | 1.63 | 2.99 | 5.48 |
SN12C | 1.70 | 3.29 | 6.36 | 1.59 | 3.04 | 5.80 | 1.58 | 2.99 | 5.66 | 1.71 | 3.25 | 6.19 |
TK-10 | 2.34 | 3.86 | 6.36 | 2.25 | 3.72 | 6.18 | 2.30 | 3.77 | 6.18 | 2.32 | 3.78 | 6.15 |
UO-31 | 1.42 | 2.73 | 5.26 | 1.40 | 2.71 | 5.23 | 1.43 | 2.75 | 5.28 | 1.69 | 3.06 | 5.53 |
Prostate Cancer | ||||||||||||
PC-3 | 1.21 | 2.58 | 5.49 | 1.26 | 2.77 | 6.11 | 1.29 | 2.77 | 5.93 | 2.56 | 10.4 | 43.6 |
DU-145 | 1.72 | 3.11 | 5.62 | 1.63 | 2.99 | 5.49 | 1.72 | 3.13 | 5.68 | 1.84 | 3.55 | 6.83 |
Breast Cancer | ||||||||||||
MCF7 | 1.78 | 4.49 | >100 | 1.33 | 3.65 | ND a | 1.54 | 3.82 | 9.44 | 1.82 | 5.33 | >100 |
MDA-MB-231/ATCC | 1.19 | 2.53 | 5.37 | 1.07 | 2.38 | 5.31 | 1.17 | 2.50 | 5.34 | 1.46 | 3.08 | 6.48 |
HS 578T | 2.27 | 5.64 | >100 | 2.11 | 5.25 | >100 | 2.22 | 5.82 | >100 | 2.43 | 5.78 | >100 |
BT-549 | 1.72 | 3.27 | 6.19 | 1.52 | 2.88 | 5.46 | 1.43 | 2.80 | 5.49 | 1.97 | 3.40 | 5.87 |
T-47D | 1.37 | ND a | >100 | 0.467 | 3.17 | >100 | 1.01 | 3.91 | >100 | 1.50 | 3.62 | 8.74 |
MDA-MB-468 | 1.52 | 3.06 | 6.16 | 1.45 | 2.88 | 5.71 | 1.49 | 2.92 | 5.75 | 1.23 | 2.57 | 5.37 |
(µM) | DU-145 | MDA-MB-231 | HCT-116 | HUVEC | |
---|---|---|---|---|---|
AQQ1 | IC50 | 4.18 ± 0.73 | 8.27 ± 0.91 | 5.83 ± 0.76 | 5.39 ± 0.73 |
AQQ2 | IC50 | 4.17 ± 0.80 | 13.33 ± 1.12 | 9.18 ± 0.96 | 6.39 ± 0.80 |
DOXO | IC50 | <100 | 59.06 ± 9.06 | 24.35 ± 6.90 | 57.48 ± 9.82 |
Source | Parameters | AQQ1 | AQQ2 | Verapamil | Atenolol |
---|---|---|---|---|---|
Log P | 1.85 | 1.77 | −0.21 | −0.33 | |
Log D | 2.37 | 2.35 | 1.87 | −1.77 | |
Mouse liver microsomes | % Metabolism in 30 min | 63 | 96.5 | 80.0 | |
Half-life (min) | 20.5 | 5.5 | 11.0 | ||
CLint (L/min/mg protein) | 68.5 | 249 | 130.0 | ||
Rat liver microsomes | % Metabolism in 30 min | 100 | 100 | 79.0 | |
Half-life (min) | 2 | 3 | 11.0 | ||
CLint (L/min/mg protein) | 655.5 | 501 | 121.0 | ||
Dog liver microsomes | % Metabolism in 30 min | 41.5 | 79.5 | 81.0 | |
Half-life (min) | 31 | 17 | 11.0 | ||
CLint (L/min/mg protein) | 45 | 84 | 131.0 | ||
Human liver microsomes | % Metabolism in 30 min | 39.5 | 47 | 79.0 | |
Half-life (min) | >30 | 26.5 | 11.0 | ||
CLint (L/min/mg protein) | 39 | 52 | 129.0 |
Parameters | AQQ1 | AQQ2 | ||
---|---|---|---|---|
IV | PO | IV | PO | |
C0 (IV only)/Cmax (PO only) (ng/mL) | 90.8 ± 71.3 | 435 ± 18.1 | 23.2 ± 12.8 | 282 ± 79.4 |
Tmax (h) | NA | 0.5 | NA | 1 |
AUClast (h × ng/mL) | 77.5 ± 9.81 | 3810 ± 111 | 77 ± 21 | 2300 ± 416 |
AUCINF (h × ng/mL) | 115 ± 45.7 | 4000 ± 179 | 110 ± 18.1 | 2370 ± 375 |
T1/2 (h) | 9.35 ± 8.75 | 5.22 ± 0.843 | 12.8 ± 2.95 | 4.72 ± 1.16 |
Vd (L/kg) | 90.3 ± 40 | NC b | 147 ± 9.71 | NC b |
Cl (mL/min/kg) | 161 ± 62.9 | NC b | 154 ± 26.9 | NC b |
MRTlast (h) | 3.77 ± 0.279 | 7.47 ± 0.367 | 6.84 ± 1.84 | 6.61 ± 0.787 |
F% | NA a | 9.83 | NAa | 5.96 |
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Jannuzzi, A.T.; Yilmaz Goler, A.M.; Biswas, A.; Mondal, S.; Basavanakatti, V.N.; Yıldırım, H.; Yıldız, M.; Bayrak, N.; Jayaprakash, V.; TuYuN, A.F. Prospects for Prostate Cancer Chemotherapy: Cytotoxic Evaluation and Mechanistic Insights of Quinolinequinones with ADME/PK Profile. Biomedicines 2024, 12, 1241. https://doi.org/10.3390/biomedicines12061241
Jannuzzi AT, Yilmaz Goler AM, Biswas A, Mondal S, Basavanakatti VN, Yıldırım H, Yıldız M, Bayrak N, Jayaprakash V, TuYuN AF. Prospects for Prostate Cancer Chemotherapy: Cytotoxic Evaluation and Mechanistic Insights of Quinolinequinones with ADME/PK Profile. Biomedicines. 2024; 12(6):1241. https://doi.org/10.3390/biomedicines12061241
Chicago/Turabian StyleJannuzzi, Ayse Tarbin, Ayse Mine Yilmaz Goler, Abanish Biswas, Subodh Mondal, Vinay N. Basavanakatti, Hatice Yıldırım, Mahmut Yıldız, Nilüfer Bayrak, Venkatesan Jayaprakash, and Amaç Fatih TuYuN. 2024. "Prospects for Prostate Cancer Chemotherapy: Cytotoxic Evaluation and Mechanistic Insights of Quinolinequinones with ADME/PK Profile" Biomedicines 12, no. 6: 1241. https://doi.org/10.3390/biomedicines12061241
APA StyleJannuzzi, A. T., Yilmaz Goler, A. M., Biswas, A., Mondal, S., Basavanakatti, V. N., Yıldırım, H., Yıldız, M., Bayrak, N., Jayaprakash, V., & TuYuN, A. F. (2024). Prospects for Prostate Cancer Chemotherapy: Cytotoxic Evaluation and Mechanistic Insights of Quinolinequinones with ADME/PK Profile. Biomedicines, 12(6), 1241. https://doi.org/10.3390/biomedicines12061241