All chemical reagents were of analytical grade, purchased from Sigma Aldrich and Alfa Aesar (USA), and used without further purification. TLC can be used to monitor the progress of a reactions, on the silica gel pre-coated chromatographic plates 60 F254 (Merck). Stuart Digital Melting Point apparatus (SMP10) and an open capillary was used to determine melting points (uncorrected). The 1H and 13C NMR (CD3OD, CDCl3 or DMSO-d6, 300 MHz, 75.0 MHz) spectra were recorded in a Varian instrument at 25 °C using tetramethylsilane (TMS) as the internal standard. An electrospray ionization mass spectrometry (ESI-HRMS) was a choice method used to record high-resolution mass spectra of all hybrids.

For the one-pot synthesis of hybrids 1a−l a modified protocol to a published method was used [47]. Commercially available isatoic anhydride (1 mmol), aldehyde (1 mmol) and 5-methoxytryptamine (1.1 mmol), were dissolved in acetic acid (5 mL). Subsequently, the reaction mixture was refluxed ( ~ 120 °C) under vigorous stirring for 1.5 h. After reaction was completed (TLC monitoring), crushed ice was added into the reaction vessel and stirred for 1 h, then aqueous potassium carbonate solution was added, and stir until the pH is adjusted to 8-9. The precipitate formed was collected by vacuum filtration, washed three times with water and oven-drying (45 °C, 3 h) to afford pure the desired hybrids 1a−l as a racemic mixture in good to excellent yields (63–93%).

3-(2-(5-methoxy-1H-indol-3-yl)ethyl)-2-phenyl-2,3-dihydroquinazolin-4(1H)-one (1a)

White solid; yield: 63%, mp: 240–242 °C. 1H NMR (300 MHz, CD3OD): δ 7.90–7.72 (m, 5H, Ar-H), 7.53–7.43 (m, 3H, Ar-H), 7.38 (d, J = 7.5 Hz, 1H, Ar-H), 7.16 (d, J = 8.8 Hz, 1H, Ar-H), 7.02 (d, J = 2.5 Hz, 1H, Ar-H), 6.78 (dd, J = 8.8, 2.5 Hz, 1H, Ar-H), 5.60 (s, 1H, C-Hquinazolinone), 3.84 (s, 3H, OCH3), 3.56–3.45 (m, 1H, N-CH2-A), 3.42–3.34 (m, 1H, N-CH2-B), 3.18–3.06 (m, 1H, N-CH2-CH2-A), 3.06–2.95 (m, 1H, N-CH2-CH2-B). 13C NMR (75 MHz, CD3OD): δ 169.6 (C = O amide), 154.0 (Ar-O), 137.0, 134.0, 132.9, 132.0, 130.3, 129.2, 129.1, 128.8, 126.6, 122.7, 111.8, 111.6, 107.9, 99.7, 57.2 (C-Hquinazolinone), 54.9 (OCH3), 41.1 (N-CH2-CH2), 19.5 (N-CH2-CH2). HRMS (ESI): m/z [M + H]+ calcd for C25H23N3O2: 398.3165; found: 398.3168.

3-(2-(5-methoxy-1H-indol-3-yl)ethyl)-2-(3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (1b)

Pale brown solid; yield: 78%, mp: 97–100 °C. 1H NMR (300 MHz, CDCl3): δ 7.94–7.86 (m, 2H, Ar-H), 7.82–7.77 (m, 2H, Ar-H), 7.60 (s, 1H, Ar-H), 7.34–7.26 (m, 1H, Ar-H), 7.16 (d, J = 8.7 Hz, 1H, Ar-H), 7.04 (d, J = 2.4 Hz, 1H, Ar-H), 6.84 (dd, J = 8.8, 2.5 Hz, 1H, Ar-H), 5.23 (s, 1H, C-Hquinazolinone), 3.91 (s, 3H, OCH3), 3.80 (s, 3H, OCH3), 3.53–3.36 (m, 1H, N-CH2-A), 3.27–3.11 (m, 1H, N-CH2-B), 3.02–2.91 (m, 1H, N-CH2-CH2-A), 2.91–2.79 (m, 1H, N-CH2-CH2-B). 13C NMR (75 MHz, CDCl3): δ 169.6 (C = O amide), 168.4 (Ar-O), 160.0 (Ar-O), 154.1, 142.7, 134.8, 134.3, 132.7, 131.1, 129.9, 127.7, 123.6, 120.8, 114.0, 113.9, 111.7, 109.9, 100.5, 57.9 (C-Hquinazolinone), 56.0 (OCH3), 55.3 (OCH3), 42.6 (N-CH2-CH2), 22.2 (N-CH2-CH2). HRMS (ESI): m/z [M + H]+ calcd for C26H25N3O3: 428.1962; found: 428.1963.

2-(3-chlorophenyl)-3-(2-(5-methoxy-1H-indol-3-yl)ethyl)-2,3-dihydroquinazolin-4(1H)-one (1c)

Pale brown solid; yield: 77%, mp: 137–140 °C. 1H NMR (300 MHz, CDCl3): δ 7.93–7.85 (m, 2H, Ar-H), 7.83–7.73 (m, 2H, Ar-H), 7.36–7.28 (m, 4H, Ar-H), 7.27–7.22 (m, 1H, Ar-H), 7.16 (d, J = 8.7 Hz, 1H, Ar-H), 7.05 (d, J = 2.5 Hz, 1H, Ar-H), 6.85 (dd, J = 8.7, 2.5 Hz, 1H, Ar-H), 5.18 (s, 1H, C-Hquinazolinone), 3.91 (s, 3H, OCH3), 3.47–3.32 (m, 1H, N-CH2-A), 3.23–3.10 (m, 1H, N-CH2-B), 3.02–2.89 (m, 1H, N-CH2-CH2-A), 2.88–2.77 (m, 1H, N-CH2-CH2-B). 13C NMR (75 MHz, CDCl3): δ 168.6 (C = O amide), 154.1 (Ar-O), 143.8, 134.7, 134.3, 134.3, 132.7, 131.1, 130.1, 128.6, 128.4, 127.6, 126.8, 123.6, 111.8, 111.7, 111.6, 110.3, 100.6, 57.4 (C-Hquinazolinone), 56.0 (OCH3), 42.4 (N-CH2-CH2), 22.4 (N-CH2-CH2). HRMS (ESI): m/z [M + H]+ calcd for C25H22ClN3O2: 432.1460; found: 432.1465.

3-(2-(5-methoxy-1H-indol-3-yl)ethyl)-2-(3-nitrophenyl)-2,3-dihydroquinazolin-4(1H)-one (1d)

Yellow solid; yield: 80%, mp: 95–97 °C. 1H NMR (300 MHz, CD3OD): δ 8.26–8.12 (m, 3H, Ar-H), 7.86–7.76 (m, 3H, Ar-H), 7.69 (d, J = 7.7 Hz, 1H, Ar-H), 7.63–7.52 (m, 2H, Ar-H), 7.12 (d, J = 8.7 Hz, 1H, Ar-H), 6.99 (d, J = 2.5 Hz, 1H, Ar-H), 6.74 (dd, J = 8.7, 2.5 Hz, 1H, Ar-H), 5.29 (s, 1H, C-Hquinazolinone), 3.83 (s, 3H, OCH3), 3.27–3.14 (m, 1H, N-CH2-A), 3.15–3.01 (m, 1H, N-CH2-B), 2.98–2.86 (m, 1H, N-CH2-CH2-A), 2.83–2.72 (m, 1H, N-CH2-CH2-B). 13C NMR (75 MHz, CD3OD): δ 169.5 (C = O amide), 153.7 (Ar-O), 148.4 (Ar-NO2), 144.0, 134.8, 133.9, 133.2, 132.9, 131.8, 129.3, 127.2, 123.3, 122.7, 122.4, 111.3, 111.1, 109.2, 99.8, 56.6 (C-Hquinazolinone), 54.9 (OCH3), 41.3 (N-CH2-CH2), 21.4 (N-CH2-CH2). HRMS (ESI): m/z [M + H]+ calcd for C25H22N4O4: 443.1957; found: 443.1961.

2-(2,3-dimethoxyphenyl)-3-(2-(5-methoxy-1H-indol-3-yl)ethyl)-2,3-dihydroquinazolin-4(1H)-one (1e)

Pale brown solid; yield: 68%, mp: 119–121 °C. 1H NMR (300 MHz, CD3OD): δ 7.89–7.74 (m, 4H, Ar-H), 7.62–7.52 (m, 1H, Ar-H), 7.12 (d, J = 8.7 Hz, 1H, Ar-H), 7.04–6.99 (m, 2H, Ar-H), 6.97 (d, J = 2.5 Hz, 1H, Ar-H), 6.71 (dd, J = 8.7, 2.5 Hz, 1H, Ar-H), 6.64 (t, J = 4.6 Hz, 1H, Ar-H), 5.47 (s, 1H, C-Hquinazolinone), 3.88 (s, 3H, OCH3), 3.83 (s, 3H, OCH3), 3.74 (s, 3H, OCH3), 3.31–3.20 (m, 1H, N-CH2-A), 3.13–3.01 (m, 1H, N-CH2-B), 2.92–2.85 (m, 1H, N-CH2-CH2-A), 2.84–2.77 (m, 1H, N-CH2-CH2-B). 13C NMR (75 MHz, CD3OD): δ 169.5 (C = O amide), 153.6 (Ar-O), 152.9 (Ar-O), 147.3 (Ar-O), 134.2, 133.9, 132.9, 131.5, 127.3, 123.7, 122.7, 121.4, 112.4, 111.2, 110.6, 108.2, 99.6, 59.7 (C-Hquinazolinone), 54.9 (OCH3), 54.8 (OCH3), 52.3 (OCH3), 41.3 (N-CH2-CH2), 21.4 (N-CH2-CH2). HRMS (ESI): m/z [M + H]+ calcd for C27H27N3O4: 458.2061; found: 458.2065.

2-(2,4-dimethoxyphenyl)-3-(2-(5-methoxy-1H-indol-3-yl)ethyl)-2,3-dihydroquinazolin-4(1H)-one (1f)

Pale brown solid; yield: 78%, mp: 97–99 °C. 1H NMR (300 MHz, CD3OD): δ 7.88–7.75 (m, 4H, Ar-H), 7.13 (d, J = 8.7 Hz, 1H, Ar-H), 6.96 (d, J = 2.4 Hz, 1H, Ar-H), 6.77–6.68 (m, 3H, Ar-H), 6.61 (d, J = 2.4 Hz, 1H, Ar-H), 6.40 (dd, J = 8.4, 2.4 Hz, 1H, Ar-H), 5.52 (s, 1H, C-Hquinazolinone), 3.88 (s, 3H, OCH3), 3.82 (s, 3H, OCH3), 3.77 (s, 3H, OCH3), 3.20–3.08 (m, 1H, N-CH2-A), 3.07–2.96 (m, 1H, N-CH2-B), 2.88–2.76 (m, 2H, N-CH2-CH2-A + N-CH2-CH2-B). 13C NMR (75 MHz, CD3OD): δ 169.6 (C = O amide), 161.0 (Ar-O), 158.4 (Ar-O), 153.6 (Ar-O), 133.9, 132.9, 131.6, 130.1, 127.3, 122.6, 121.2, 111.1, 110.5, 108.6, 103.7, 99.6, 98.1, 54.9 (OCH3), 54.6 (OCH3), 54.4 (OCH3), 50.4 (C-Hquinazolinone), 40.0 (N-CH2-CH2), 21.3 (N-CH2-CH2). HRMS (ESI): m/z [M + H]+ calcd for C27H27N3O4: 458.2067; found: 458.2072.

2-(3-hydroxy-4-methoxyphenyl)-3-(2-(5-methoxy-1H-indol-3-yl)ethyl)-2,3-dihydroquinazolin-4(1H)-one (1g)

Pale brown solid; yield: 77%, mp: 137–139 °C. 1H NMR (300 MHz, CD3OD): δ 7.88–7.72 (m, 4H, Ar-H), 7.66–7.49 (m, 1H, Ar-H), 7.12 (d, J = 8.7 Hz, 1H, Ar-H), 6.96 (d, J = 2.4 Hz, 1H, Ar-H), 6.92 (d, J = 8.1 Hz, 1H, Ar-H), 6.80–6.73 (m, 2H, Ar-H), 6.71 (dd, J = 8.7, 2.4 Hz, 1H, Ar-H), 5.10 (s, 1H, C-Hquinazolinone), 3.84 (s, 3H, OCH3), 3.83 (s, 3H, OCH3), 3.30–3.20 (m, 1H, N-CH2-A), 3.16–2.99 (m, 1H, N-CH2-B), 2.98–2.75 (m, 2H, N-CH2-CH2-A + N-CH2-CH2-B). 13C NMR (75 MHz, CD3OD): δ 169.6 (C = O amide), 153.6 (Ar-O), 147.7 (Ar-O), 146.3 (Ar-OH), 134.0, 132.9, 129.6, 129.4, 122.7, 120.0, 115.4, 111.2, 110.7, 108.3, 99.7, 56.9 (C-Hquinazolinone), 55.0 (OCH3), 54.9 (OCH3), 41.3 (N-CH2-CH2), 21.2 (N-CH2-CH2). HRMS (ESI): m/z [M + H]+ calcd for C26H25N3O4: 444.1174; found: 444.1179.

2-(4-hydroxy-3-methoxyphenyl)-3-(2-(5-methoxy-1H-indol-3-yl)ethyl)-2,3-dihydroquinazolin-4(1H)-one (1h)

Pale orange solid; yield: 81%, mp: 211–213 °C. 1H NMR (300 MHz, DMSO-d6): δ 7.85–7.76 (m, 3H, Ar-H), 7.10 (d, J = 8.7 Hz, 1H, Ar-H), 6.92–6.82 (m, 3H, Ar-H), 6.71 (d, J = 8.1 Hz, 1H, Ar-H), 6.63 (dd, J = 8.7, 2.2 Hz, 3H, Ar-H), 4.96 (s, 1H, C-Hquinazolinone), 3.74 (s, 3H, OCH3), 3.72 (s, 3H, OCH3), 3.20–3.01 (m, 1H, N-CH2-A), 2.97–2.82 (m, 1H, N-CH2-B), 2.77–2.55 (m, 2H, N-CH2-CH2-A + N-CH2-CH2-B). 13C NMR (75 MHz, DMSO-d6): δ 169.8 (C = O amide), 153.4 (Ar-O), 147.8 (Ar-O), 146.3 (Ar-OH), 137.2, 134.8, 134.4, 133.1, 131.4, 127.6, 123.4, 121.1, 115.4, 113.0, 112.1, 110.5, 108.2, 100.2, 57.3 (C-Hquinazolinone), 56.0 (OCH3), 55.8 (OCH3), 42.2 (N-CH2-CH2), 22.8 (N-CH2-CH2). HRMS (ESI): m/z [M + H]+ calcd for C26H25N3O4: 444.1911; found: 444.1916.

2-(3,4-dimethoxyphenyl)-3-(2-(5-methoxy-1H-indol-3-yl)ethyl)-2,3-dihydroquinazolin-4(1H)-one (1i)

Pale brown solid; yield: 75%, mp: 114–116 °C. 1H NMR (300 MHz, CD3OD): δ 7.87–7.74 (m, 5H, Ar-H), 7.10 (d, J = 8.7 Hz, 1H, Ar-H), 6.95 (d, J = 1.9 Hz, 1H, Ar-H), 6.89 (d, J = 7.3 Hz, 1H, Ar-H), 6.88 (s, 1H, Ar-H), 6.74 (dd, J = 8.2, 1.9 Hz, 1H, Ar-H), 6.63 (dd, J = 8.7, 2.5 Hz, 1H, Ar-H), 5.00 (s, 1H, C-Hquinazolinone), 3.74 (s, 3H, OCH3), 3.73 (s, 3H, OCH3), 3.71 (s, 3H, OCH3), 3.16–3.05 (m, 1H, N-CH2-A), 2.99–2.84 (m, 1H, N-CH2-B), 2.75–2.66 (m, 1H, N-CH2-CH2-A), 2.66–2.55 (m, 1H, N-CH2-CH2-B). 13C NMR (75 MHz, CD3OD): δ 169.8 (C = O amide), 153.4 (Ar-O), 149.0 (Ar-O), 148.5 (Ar-O), 137.0, 136.0, 134.8, 133.1, 131.4, 127.6, 123.4, 120.8, 112.6, 112.1, 111.8, 110.6, 108.3, 100.2, 57.2 (C-Hquinazolinone), 56.0 (OCH3), 55.9 (OCH3), 55.8 (OCH3), 42.1 (N-CH2-CH2), 22.7 (N-CH2-CH2). HRMS-ESI (m/z): 458.2051 [M + H]+ calcd. for C27H27N3O4: 458.2054.

2-(3,5-dimethoxyphenyl)-3-(2-(5-methoxy-1H-indol-3-yl)ethyl)-2,3-dihydroquinazolin-4(1H)-one (1j)

Pale brown solid; yield: 93%, mp: 150–152 °C. 1H NMR (300 MHz, DMSO-d6): δ 7.89–7.71 (m, 4H, Ar-H), 7.12 (d, J = 8.7 Hz, 1H, Ar-H), 6.89 (s, 1H, Ar-H), 6.64 (dd, J = 8.7, 2.5 Hz, 1H, Ar-H), 6.53–6.30 (m, 4H, Ar-H), 4.98 (s, 1H, C-Hquinazolinone), 3.74 (s, 3H, OCH3), 3.70 (s, 6H, 2 x OCH3), 3.19–3.02 (m, 1H, N-CH2-A), 2.99–2.82 (m, 1H, N-CH2-B), 2.78–2.55 (m, 2H, N-CH2-CH2-A + N-CH2-CH2-B). 13C NMR (75 MHz, DMSO-d6): δ 170.0 (C = O amide), 160.7 (2 x Ar-O), 153.4 (Ar-O), 145.9, 136.5, 134.7, 133.2, 131.4, 127.6, 123.3, 112.1, 110.7, 108.3, 106.9, 100.2, 99.3, 57.4 (C-Hquinazolinone), 55.8 (OCH3), 55.6 (2 x OCH3), 42.1 (N-CH2-CH2), 22.7 (N-CH2-CH2). HRMS-ESI (m/z): 458.2066 [M + H]+ calcd. for C27H27N3O4: 458.2069.

3-(2-(5-methoxy-1H-indol-3-yl)ethyl)-2-(3,4,5-trimethoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (1k)

Pale brown solid; yield: 81%, mp: 92–94 °C. 1H NMR (300 MHz, DMSO-d6): δ 7.87–7.78 (m, 4H, Ar-H), 7.12 (d, J = 8.7 Hz, 1H, Ar-H), 6.89 (d, J = 2.4 Hz, 1H, Ar-H), 6.69–6.64 (m, 3H, Ar-H), 6.62 (d, J = 2.4 Hz, 1H, Ar-H), 5.00 (s, 1H, C-Hquinazolinone), 3.74 (s, 3H, OCH3), 3.72 (s, 6H, 2 x OCH3), 3.65 (s, 3H, OCH3), 3.26–3.10 (m, 1H, N-CH2-A), 3.00–2.86 (m, 1H, N-CH2-A), 2.80–2.67 (m, 1H, N-CH2-CH2-A), 2.65–2.55 (m, 1H, N-CH2-CH2-B). 13C NMR (75 MHz, DMSO-d6): δ 169.9 (C = O amide), 153.4 (Ar-O), 153.1 (2 x Ar-O), 139.1 (Ar-O), 137.1, 136.8, 134.8, 133.1, 131.4, 127.6, 123.4, 112.1, 110.6, 108.2, 105.9, 100.2, 60.4 (C-Hquinazolinone), 58.0 (OCH3), 56.2 (2 x OCH3), 55.8 (OCH3), 42.7 (N-CH2-CH2), 22.7 (N-CH2-CH2). HRMS (ESI): m/z [M + H]+ calcd for C28H29N3O5: 488.2076; found: 488.2079.

2-(4-hydroxy-3,5-dimethoxyphenyl)-3-(2-(5-methoxy-1H-indol-3-yl)ethyl)-2,3-dihydroquinazolin-4(1H)-one (1l)

Pale red solid; yield: 82%, mp: 161–163 °C. 1H NMR (300 MHz, DMSO-d6): δ 7.89–7.78 (m, 5H, Ar-H), 7.11 (d, J = 8.7 Hz, 1H, Ar-H), 6.89 (d, J = 2.5 Hz, 1H, Ar-H), 6.63 (dd, J = 8.7, 2.5 Hz, 1H, Ar-H), 6.60–6.56 (m, 2H, Ar-H), 4.96 (s, 1H, C-Hquinazolinone), 3.74 (s, 3H, OCH3), 3.70 (s, 6H 2 x OCH3), 3.26–3.13 (m, 1H, N-CH2-A), 2.98–2.84 (m, 1H, N-CH2-B), 2.78–2.63 (m, 1H, N-CH2-CH2-A), 2.66–2.54 (m, 1H, N-CH2-CH2-B). 13C NMR (75 MHz, DMSO-d6): δ 169.8 (C = O amide), 153.4 (Ar-O), 148.2 (2 x Ar-O), 137.2 (Ar-OH), 135.3, 134.8, 133.4, 133.1, 131.4, 127.7, 123.4, 112.1, 110.5, 108.1, 106.3, 100.3, 57.9 (C-Hquinazolinone), 56.4 (2 x OCH3), 55.8 (OCH3), 42.7 (N-CH2-CH2), 22.7 (N-CH2-CH2). HRMS (ESI): m/z [M + H]+ calcd for C27H27N3O5: 474.1918; found: 474.1922.

Human colorectal adenocarcinoma cells (SW480) and a normal human colon mucosal epithelial cell line (NCM460) from the European Collection of Authenticated Cell Cultures (ECACC, UK) were used to study the chemopreventive potential of the new quinazolinone/melatonin hybrids. The cells were maintained in Dulbecco’s Modified Eagle Medium (DMEM), which was supplemented with 10% horse serum that had been previously inactivated at 56 °C, 1% non-essential amino acids, and 1% antibiotics (streptomycin and penicillin; Gibco Invitrogen, Carlsbad, CA, USA). Horse serum was lowered to 3% for each experiment, and ITS defined medium (Gibco, Invitrogen, Carlsbad, CA, USA) with 10 mg/mL insulin, 5 mg/mL transferrin, and 5 ng/mL selenium was added to the culture media as well [64].

The effect of the hybrids on cell viability was assessed using the Sulforhodamine B (SRB) colorimetric technique. Before the monolayer reached 100% confluence, the cell density was adjusted to 10,000 cells/well in 96-well tissue culture plates, which had previously been standardized to guarantee the cells’ exponential phase during the experiment. Following this, the cells were incubated for a full day before being treated every day for the next 24 to 48 h with progressively higher concentrations (0.6 to 40 µM) of the various compounds. We used different controls in this investigation in addition to the hybrid molecules. The first one (vehicle control) established the baseline for the tests by solubilizing the chemicals in DMSO (0.5%). Furthermore, we employed the parental compound (melatonin) and the reference drug (5-FU). The ideal parameters were 5% CO2 and 37 °C. After each treatment, culture plates were left at 4 °C for one hour with 50% v/v of cold trichloroacetic acid (MERCK), to fix the cells. Next, the cell protein content was stained using 0.4% (w/v) SRB (Sigma-Aldrich, St. Louis, MO, USA). Five washes using 1% acetic acid were employed to remove any unbound SRB. Before solubilizing in 10 mM Tris-base and measuring the absorbance at 492 nm using a Mindray MR-96A microplate reader, protein-bound SRB was allowed to air dry. Each experiment was conducted thrice [65, 66].

The experimental design included at least three repetitions for each measurement. The information was displayed as mean ± SE, or standard error. Following the two-way ANOVA statistical analysis, Tukey’s test was conducted. Values of p < 0.05 were considered significant. GraphPad Prism version 8.0.1 for (Graph Pad Software, San Diego, CA, USA) was used to analyze the data.

The most promising hybrids 1i (3,4-dimethoxy) and 1j (3,5-dimethoxy) were screened for their ADME-tox profile using the opensource cheminformatics toolkits SwissADME [67]. For 1i and 1j, eleven biopharmaceutical relevant properties were accessed: Topographical polar surface area (TPSA), MW and rotatable bonds, logPo/w, the number of H-donors/H-acceptors, the fraction of sp3 carbon atoms, and the number of aromatic/heteroaromatic rings. Finally, SwissADME was also used for investigating substructural alerts to identify pan-assay interference compounds (PAINS). Note that, these important biopharmaceutical parameters govern oral exposure, as well as permeability, absorption, motion and action of potential drug candidates. Further, we explored the toxicological profile for 1i and 1j using eight in silico freeware platforms such as SwissADME [67], OSIRIS [68], T.E.S.T Version 5.1.2 [69], ProTox-II [70], Pred-Herg [71], pkCSM [72], ToxTree [73], and ADMET-SAR [74].

Supporting information

Supplementary material provides copy of the NMR spectra (1H-NMR and 13C-NMR) and ESI-HRMS of quinazolinone-MLT conjugates 1a–l.