Synthesis, molecular modeling simulations and anticancer activity of some new Imidazo[2,1-b]thiazole analogues as EGFR/HER2 and DHFR inhibitors.

New imidazo[2,1-b]thiazole analogs were designed, synthesized, and biologically evaluated as anticancer agents. In vitro biological evaluation of the anticancer properties of the compounds was performed against different cancer cell lines. Compounds 23 and 39 showed remarkable broad -spectrum cytotoxic potency on most of the tested cell lines. Compounds 23 and 39 exhibited potent activity against the MCF-7 breast cancer cell line, with IC50 values of 1.81 and 4.95 µM, respectively, compared to DOX and SOR (IC50 values of 4.17 and 7.26 µM, respectively). An enzyme inhibition assay was carried out to clarify the possible mode of action of the tested compounds. Compounds 23 and 39 were identified as possible EGFR, HER-2, and DHFR inhibitors. Cell cycle arrest results indicated that compound 23 caused cell cycle arrest at the G0/G1 phase in the MCF-7 cells and at the G2/M phase in the Hep G2 cells. Compound 39 induced cell cycle arrest at the G2/M phase in Hela cells. In vivo testing of the anticancer activity of the two most promising molecules in this study was conducted, and the results indicated that they possess considerable in vivo anticancer activity in mice. Data obtained from the molecular modeling simulation study were consistent with the biological evaluation results.

Tetraenone A: A New ß-Ionone Derivative from Tetraena aegyptia.

In this study, the chemical investigation of Tetraena aegyptia (Zygophyllaceae) led to the identification of a new megastigmene derivative, tetraenone A ((2S, 5R, 6R, 7E)-2-hydroxy-5,6-dihydro-ß-ionone) (1), along with (3S, 5R, 6S, 7E)-3-hydroxy-5,6-epoxy-5,6-dihydro-ß-ionone- (2), 3,4-dihydroxy-cinnamyl alcohol-4-glucoside (3), 3ß,19α-dihydroxy-ursan-28-oic acid (4), quinovic acid (5), p-coumaric acid (6), and ferulic acid (7), for the first time. The chemical structures of 1-7 were confirmed by analysis of their 1D and 2D NMR and HRESIMS spectra and by their comparison with the relevant literature. The absolute configurations of 1 and 2 were assigned based on NOESY interactions and ECD spectra. Conformational analysis showed that 1 existed exclusively in one of the two theoretically possible chair conformers with a predominant s-trans configuration for the 3-oxobut-1-en-1-yl group with the ring, while the half-chair conformer had a pseudo-axial hydroxy group that was predominant over the other half-chair conformation. Boat conformations were not among the most stable conformations, and the s-trans isomerism was in favor of s-cis configuration. In silico investigation revealed that 1 and 2 had more favorable binding interactions with Mpro rather than with TMPRSS2. Accordingly, molecular dynamic simulations were performed on the complexes of compounds 1 and 2 with Mpro to explore the stability of their interaction with the target protein structure. Compounds 1 and 2 might offer a possible starting point for developing covalent inhibitors of Mpro of SARS-CoV-2.

Design, Synthesis, In Vitro, and In Silico Studies of New N5-Substituted-pyrazolo[3,4-d]pyrimidinone Derivatives as Anticancer CDK2 Inhibitors.

CDK2 is a key player in cell cycle processes. It has a crucial role in the progression of various cancers. Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are two common cancers that affect humans worldwide. The available therapeutic options suffer from many drawbacks including high toxicity and decreased specificity. Therefore, there is a need for more effective and safer therapeutic agents. A series of new pyrazolo[3,4-d]pyrimidine analogs was designed, synthesized, and evaluated as anticancer agents against the CRC and HCC cells, HCT116, and HepG2, respectively. Pyrazolo[3,4-d]pyrimidinone derivatives bearing N5-2-(4-halophenyl) acetamide substituents were identified as the most potent amongst evaluated compounds. Further evaluation of CDK2 kinase inhibition of two potential cytotoxic compounds 4a and 4b confirmed their CDK2 inhibitory activity. Compound 4a was more potent than the reference roscovitine regarding the CDK2 inhibitory activity (IC50 values: 0.21 and 0.25 µM, respectively). In silico molecular docking provided insights into the molecular interactions of compounds 4a and 4b with important amino acids within the ATP-binding site of CDK2 (Ile10, Leu83, and Leu134). Overall, compounds 4a and 4b were identified as interesting CDK2 inhibitors eliciting antiproliferative activity against the CRC and HCC cells, HCT116 and HepG2, respectively, for future further investigations and development.

Design, Synthesis, and Repurposing of Rosmarinic Acid-ß-Amino-α-Ketoamide Hybrids as Antileishmanial Agents.

A series of rosmarinic acid-ß-amino-α-ketoamide hybrids were synthesized and rationally repurposed towards the identification of new antileishmanial hit compounds. Two hybrids, 2g and 2h, showed promising activity (IC50 values of 9.5 and 8.8 µM against Leishmania donovani promastigotes, respectively). Their activities were comparable to erufosine. In addition, cytotoxicity evaluation employing human THP-1 cells revealed that the two hybrids 2g and 2h possess no cytotoxic effects up to 100 µM, while erufosine possessed cytotoxicity with CC50 value of 19.4 µM. In silico docking provided insights into structure-activity relationship emphasizing the importance of the aliphatic chain at the α-carbon of the cinnamoyl carbonyl group establishing favorable binding interactions with LdCALP and LARG in both hybrids 2g and 2h. In light of these findings, hybrids 2g and 2h are suggested as potential safe antileishmanial hit compounds for further development of anti-leishmanial agents.

Repurposing Synthetic Congeners of a Natural Product Aurone Unveils a Lead Antitumor Agent Inhibiting Folded P-Loop Conformation of MET Receptor Tyrosine Kinase.

A library of 24 congeners of the natural product sulfuretin were evaluated against nine panels representing nine cancer diseases. While sulfuretin elicited very weak activities at 10 µM concentration, congener 1t was identified as a potential compound triggering growth inhibition of diverse cell lines. Mechanistic studies in HCT116 colon cancer cells revealed that congener 1t dose-dependently increased levels of cleaved-caspases 8 and 9 and cleaved-PARP, while it concentration-dependently decreased levels of CDK4, CDK6, Cdc25A, and Cyclin D and E resulting in induction of cell cycle arrest and apoptosis in colon cancer HCT116 cells. Mechanistic study also presented MET receptor tyrosine kinase as the molecular target mediating the anticancer activity of compound 1t in HCT116 cells. In silico study predicted folded p-loop conformation as the form of MET receptor tyrosine kinase responsible for binding of compound 1t. Together, the current study presents compound 1t as an interesting anticancer lead for further development.

Multi-targeted anti-Alzheimer's agents: Synthesis, biological evaluation, and molecular modeling study of some pyrazolopyridine hybrids.

A new series of compounds bearing a pyrazolopyridine scaffold was synthesized as integrated anti-Alzheimer's disease (AD) multi-targeted ligands. Compounds 49 and 51 showed remarkable activity as hAChE inhibitors with IC50 values of 0.17 and 0.16 µM, respectively; and proved to be active hBuChE inhibitors with IC50 values 0.17 and 0.69 µM, eight and two-fold more active than the reference compound rivastigmine, respectively. Compounds 49 and 51 showed potent GSK3ß inhibition with IC50 values of 0.21 and 0.26 µM, respectively compared to L807mts. Also, 49 and 51 showed 66.0 and 60.0% as tau protein aggregation inhibitors; and Aß1-42 self-aggregation inhibitors with 79.0 and 75.0% respectively. Furthermore, 49 and 51 could bind virtually with the PAS affecting Aß aggregation, thus preventing Aß-dependent neurotoxicity. They proved to have the ability to chelate bio-metals such as Fe2+, Cu2+, and Zn2+ preventing their oxidative damage in the brain of AD patients, in addition to their safety upon WI-38 cell line. Both compounds could virtually penetrate BBB and obeyed Lipinski's rule of five. Compounds 49 and 51 could be considered as MTDLs for AD patients and the obtained model and pattern of substitution could be used for further development of new multi-targeted anti-Alzheimer's agents.

New 2-alkoxycyanopyridine derivatives as inhibitors of EGFR, HER2, and DHFR: Synthesis, anticancer evaluation, and molecular modeling studies.

New series of substituted 2-alkoxycyanopyridine derivatives were synthesized and evaluated for their in vitro and in vivo anticancer activities. Comparing the evaluated activities against cancer cell lines to the broad-spectrum anticancer doxorubicin, and the kinase inhibitor sorafenib, compounds 3a, 4b, 4c, 7a, and 8d demonstrated superior anticancer efficacy with elevated safety profiles and selectivity indices, particularly against MCF7 breast cancer. For exploration of their mechanism of action, assays for inhibition of EGFR, HER2 kinase, and DHFR were performed. The promising synthesized compounds exhibited potent dual kinase EGFR/HER2 inhibitory activity with IC50values of 0.248/0.156 µM for 4b and 0.138/0.092 µM for 4c. Additionally, with IC50 values of 0.138 and 0.193 M, respectively, 4b and 4c had the greatest DHFR inhibitory activity that was comparable to methotrexate. In the MCF7 breast cancer cell line, they caused arrest at the S phase of the cell cycle and exhibited apoptosis induction activity. With restored caspase-3 immunoexpression, the anti-breast cancer assay performed in vivo of 4b and 4c demonstrated a substantial decrease in tumor volume. Results from molecular modeling were in agreement with biological assays proving the importance of the 3-caynopyridine, two substituted phenyl rings attached to central pyridine ring, and propoxy side chain moieties for binding with the receptors. As 4c works by inhibiting both EGFR/HER2 kinase, DHFR enzymes, in addition to cellular apoptosis, it could be viewed as a model of compounds possessing a multi-targeting anticancer activity. Collectively, compounds 4b and 4c might represent prototypes for further development as anticancer molecules.

Small Molecules Incorporating Privileged Amidine Moiety as Potential Hits Combating Antibiotic-Resistant Bacteria.

The continuing need for the discovery of potent antibacterial agents against antibiotic-resistant pathogens is the driving force for many researchers to design and develop such agents. Herein, we report the design, synthesis, and biological evaluation of amidine derivatives as new antibacterial agents. Compound 13d was the most active in this study against a wide range of antibiotic-resistant, and susceptible, Gram-positive, and Gram-negative bacterial strains. Time-kill assay experiments indicated that compound 13d was an effective bactericidal compound against the tested organisms at the log-phase of bacterial growth. Docking simulations were performed to assess in silico its mode of action regarding UPPS, KARI, and DNA as potential bacterial targets. Results unveiled the importance of structural features of compound 13d in its biological activity including central thiophene ring equipped with left and right pyrrolo[2,3-b]pyridine and phenyl moieties and two terminal amidines cyclized into 4,5-dihydro-1H-imidazol-2-yl functionalities. Collectively, compound 13d represents a possible hit for future development of potent antibacterial agents.

Design, synthesis, and evaluation of new anti-inflammatory natural products amide derivatives endowed with anti-blood cancer activity towards development of potential multifunctional agents against hematological cancers.

New amide derivatives of the natural product 5,6,7-trimethoxyflavanone were designed as multifunctional antiproliferative molecules against blood cancer and the associated inflammatory conditions. The targeted compounds were synthesized efficiently in three linear steps employing known chalcone starting materials. Compounds 2h, 2i, 2l, 2t, 2v and 2x having bromo or nitro substituted-phenyl rings elicited potential inhibitory effects on macrophages production of nitric oxide, PGE2 and TNF-α which are proinflammatory mediators involved in tumorigenesis and progression of blood cancer. Additionally, evaluation of direct inhibitory effects on the growth of diverse blood cancers including leukemia, lymphoma, and myeloma cell lines unveiled compound 2v as the most potential molecules eliciting at least five-folds the potency of the standard imatinib drug over the used diverse blood cancers. Furthermore, compound 2v showed good selectivity to blood cancer cells rather than normal MRC5 cells. Moreover, compound 2v triggered death of HL60 leukemia cells via apoptosis induction. In conclusion, the natural product-derived compound 2v might serve as a multifunctional lead compound for further development of agents for treatment of blood cancers.

Rational repurposing, synthesis, in vitro and in silico studies of chromone-peptidyl hybrids as potential agents against Leishmania donovani.

A chromone-peptidyl hybrids series was synthesised and rationally repurposed towards identification of potential antileishmanial hits against visceral leishmaniasis. Three hybrids 7c, 7n, and 7h showed potential IC50 values (9.8, 10, and 12 µM, respectively) which were comparable to erufosine IC50 (9.8 µM) but lower potency than miltefosine IC50 (3.5 µM). Preliminary assessment of cytotoxicity using human THP-1 cells presented chromone-peptidyl hybrids 7c and 7n as non-cytotoxic up to 100 µM while erufosine and miltefosine had CC50 of 19.4 µM and >40 µM, respectively. In silico studies pinpointed the N-p-methoxyphenethyl substituent at the peptidyl moiety together with the oxygen-based substituted functions of the phenyl ring of the chromone moiety as crucial players in binding to LdCALP. Together, these findings present chromone-peptidyl hybrids 7c and 7n as potential and anticipated non-cytotoxic antileishmanial hit compounds for possible development of potential antileishmanial agents against visceral leishmaniasis.

In Silico and In Vitro Evaluation of Some Amidine Derivatives as Hit Compounds towards Development of Inhibitors against Coronavirus Diseases.

Coronaviruses, including SARS-CoV-2, SARS-CoV, MERS-CoV and influenza A virus, require the host proteases to mediate viral entry into cells. Rather than targeting the continuously mutating viral proteins, targeting the conserved host-based entry mechanism could offer advantages. Nafamostat and camostat were discovered as covalent inhibitors of TMPRSS2 protease involved in viral entry. To circumvent their limitations, a reversible inhibitor might be required. Considering nafamostat structure and using pentamidine as a starting point, a small set of structurally diverse rigid analogues were designed and evaluated in silico to guide selection of compounds to be prepared for biological evaluation. Based on the results of in silico study, six compounds were prepared and evaluated in vitro. At the enzyme level, compounds 10-12 triggered potential TMPRSS2 inhibition with low micromolar IC50 concentrations, but they were less effective in cellular assays. Meanwhile, compound 14 did not trigger potential TMPRSS2 inhibition at the enzyme level, but it showed potential cellular activity regarding inhibition of membrane fusion with a low micromolar IC50 value of 10.87 µM, suggesting its action could be mediated by another molecular target. Furthermore, in vitro evaluation showed that compound 14 inhibited pseudovirus entry as well as thrombin and factor Xa. Together, this study presents compound 14 as a hit compound that might serve as a starting point for developing potential viral entry inhibitors with possible application against coronaviruses.

Hydrazinecarbonyl-thiazol-2-acetamides with pronounced apoptotic behavior: synthesis, in vitro/in vivo anti-proliferative activity and molecular modeling simulations.

A new series of N-[4-(2-substituted hydrazine-1-carbonyl)thiazole-2-yl]acetamides was synthesized and evaluated in vitro against six human cell lines as antitumor agents. Compounds 20, 21 and 22 showed remarkable inhibition to HeLa (IC50 values of 1.67, 3.81, 7.92 µM) and MCF-7 (IC50 values of 4.87, 5.81, 8.36 µM, respectively) cell growth with high selectivity indices and safety profiles. Compound 20 showed significant decreases in both tumor volume and body weight gain compared to vehicle control, in the solid tumor animal model of Ehrlich ascites carcinoma (EAC) with recovered caspase-3 immuno-expression. Flow cytometry cell analysis showed that 20 exerts anti-proliferative activity in mutant Hela and MCF-7 cell lines through arresting the cell growth at the G1/S phase producing cell death via apoptosis rather than necrosis. To explain the antitumor mode of action of the most active compounds, EGFR-TK and DHFR inhibition assays were carried out. Compound 21 conveyed dual EGFR/DHFR inhibition with IC50 0.143 (EGFR) and 0.159 (DHFR) µM. Compound 20 showed DHFR inhibition with IC50 0.262 µM. Compound 22 exhibited the best EGFR inhibitory efficacy with IC50 0.131 µM. Molecular modelling study revealed that 21 and 22 have binding interactions with EGFR amino acid residues Lys745 and Asp855. Compounds 20 and 21 showed affinity toward DHFR amino acid residues Asn64, Ser59 and Phe31. The ADMET profile and Lipinski's rule of five calculated for these compounds were acceptable. Compounds 20, 21 and 22 could be regarded as promising prototype antitumor agents for further optimization.

Design, synthesis, and repurposing of O6-aminoalkyl-sulfuretin analogs towards discovery of potential lead compounds as antileishmanial agents.

Up to date, there are still significantly unmet clinical needs for treatment of the fatal visceral leishmaniasis; a neglected tropical disease. Herein, a recently reported antileishmanial hit sulfuretin analog suffering from a low potency and a problematic aqueous solubility that hindered further development was used as a starting point. A mitigation rational via incorporation of O6-aminoalkyl moiety suggest structures analogous to literature-known compounds as cholinesterase inhibitors. Consequently, preparation and repurposing of a library of these compounds unveiled their potential activity against the parasite Leishmania donovani promastigotes. Further evaluation against intracellular form of the parasite and host cells suggested compounds 2a, 2c, and 2o derived from sulfuretin analogs bearing 2'-methoxy or 2',5'-dimethoxy substituents at ring-B as promising lead compounds with potential activity and acceptable safety window relative to the standard edelfosine. In silico simulation predicted plausible binding modes of these compounds to L. donovani fumarate reductase. Together this work presents compound 2o as a potential lead compound for further development.

Bestatin analogs-4-quinolinone hybrids as antileishmanial hits: Design, repurposing rational, synthesis, in vitro and in silico studies.

Amongst different forms of leishmaniasis, visceral leishmaniasis caused by L. donovani is highly mortal. Identification of new hit compounds might afford new starting points to develop novel therapeutics. In this lieu, a rationally designed small library of bestatin analogs-4-quinolone hybrids were prepared and evaluated. Analysis of SAR unveiled distinct profiles for hybrids type 1 and type 2, which might arise from their different molecular targets. Amongst type 1 bestatin analog-4-quinolone hybrids, hybrid 1e was identified as potential hit inhibiting growth of L. donovani promastigotes by 91 and 53% at 50 and 25 µM concentrations, respectively. Meanwhile, hybrid 2j was identified amongst type 2 bestatin analog-4-quinolone hybrids as potential hit compound inhibiting growth of L. donovani promastigotes by 50 and 38% at 50 and 25 µM concentrations, respectively. Preliminary safety evaluation of the promising hit compounds showed that they are 50-100 folds safer against human derived monocytic THP-1 cells relative to the drug erufosine. In silico study was conducted to predict the possible binding of hybrid 1e with methionine aminopeptidases 1 and 2 of L. donovani. Molecular dynamic simulations verified the predicted binding modes and provide more in depth understanding of the impact of hybrid 1e on LdMetAP-1 and LdMetAP-2.

Synthesis, biological evaluation, and molecular modeling studies of new benzoxazole derivatives as PARP-2 inhibitors targeting breast cancer.

Many benzoxazole-based and similar scaffolds were reported to have wide-range of anticancer activities. In this study, four series of benzoxazole derivatives were designed by combining benzoxazole scaffold with different amines via a reversed phenyl amide linker to produce the compounds of series A, B and C. A fourth new hybrid of benzoxazole with 1,2,3 triazole ring (series D) was also designed. The designed compounds were synthesized and screened for their anti-breast cancer activity against MDA-MB-231 and MCF-7 cell lines using MTT assay. The most potent cytotoxic compounds; 11-14, 21, 22, 25-27 were further evaluated for their in vitro PARP-2 enzyme inhibition. Compounds 12 and 27 proved to be the most active PARP-2 inhibitors with IC50 values of 0.07 and 0.057 µM, respectively. Compounds 12 and 27 caused cell cycle arrest in mutant MCF-7 cell line at G2/M and G1/S phase, respectively and they possessed significant apoptosis-promoting activity. Docking results of compounds 12 and 27 into PARP-2 pocket demonstrated binding interactions comparable to those of olaparib. Their predicted pharmacokinetic parameters and oral bioavailability appeared to be appropriate. Collectively, it could be concluded that compounds 12 and 27 are promising anti-breast cancer agents that act as PARP-2 inhibitors with potent apoptotic activity.

New phthalimide-based derivatives as EGFR-TK inhibitors: Synthesis, biological evaluation, and molecular modeling study.

A novel series of phthalimide derivatives was synthesized and evaluated for in vitro antitumor activity against six human cancer cell lines; HepG-2, HCT-116, MCF-7, Hep2, PC3 and Hela.The obtained results revealed that compound 32 was the most potent antitumor, while compounds 33, 22 and 24 showed strong activity against all tested cell lines. Further biological evaluation of the most active compounds was done and their in vitro EGFR-TK inhibition was tested, and the results came in accordance with the results of antitumor testing, where 32 displayed promising inhibitory activity (IC50 = 0.065 µM) compared to the standard drug erlotinib (IC50 = 0.067 µM). In addition, compounds 48, 22, 28 and 19 showed strong inhibitory activity (IC50 = 0.089, 0.093, 0.147 and 0.152 µM respectively). Cell cycle analysis was conducted and the results revealed that 32 induced cell cycle arrest on Hela and MCF-7 at G0-G1 phase and Pre-G1 phase causing cell death mainly via apoptosis. Additionally, in vivo antitumor screening revealed that 32 reduced both body weight and tumor volume in solid tumor utilizing Ehrlich ascites carcinoma (EAC) animal model. Molecular modeling study showed that 32 and 48 have the highest affinity for binding with the active site of EGFR-TK with docking score comparable to erlotinib. Compounds 32 and 48 could be used as template models for further optimization.

Thiazole-based SARS-CoV-2 protease (COV Mpro ) inhibitors: Design, synthesis, enzyme inhibition, and molecular modeling simulations.

As an attempt to contribute to the efforts of combating the pandemic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for COVID-19, new analogs of the repurposed drug nitazoxanide which showed promising inhibitory efficacy on a viral protease enzyme were designed, synthesized and evaluated for their inhibitory activity on the main protease of the SARS-CoV-2 virus, using the COV2-3CL protease inhibition assay. The obtained results showed that the N-(substituted-thiazol-2-yl)cinnamamide analogs 19, 20, and 21 were the most active compounds with IC50 values of 22.61, 14.7, 21.99 µM, respectively, against the viral protease compared to the reference drugs, nitazoxanide, and lopinavir. Molecular modeling studies showed binding interactions of 19, 20, and 21 with hydrogen bonds to Gln189 and Glu166, arene-arene interaction between the thiazole moiety and His41, and other hydrophobic interactions between the ethene spacer moiety and Asn142. Moreover, an extra arene-arene interaction between substituted benzo[d]thiazole and His41 was observed regarding compounds 19 and 21. Surface mapping and flexible alignment proved the structural similarity between the new drug candidates and nitazoxanide. Compliance of the new compounds to Lipinski's rule of five was investigated and absorption, distribution, metabolism, excretion, and toxicology data were predicted. The newly synthesized compounds are promising template ligands for further development and optimization.

DNA binding studies of novel diazatruxenones analogs as potential anticancer agents: Synthesis, antitumor investigation, DNA binding, SAR and molecular modeling calculation.

A series of polycyclic skeleton of truxene and triazatruxene analogs has been synthesized and evaluated for antitumor and DNA binding activities. The synthesized structures were confirmed by different spectroscopic techniques such as IR, 1HNMR, 13CNMR, and mass spectroscopy. The antitumor screening was performed adopting the NCI protocol against 60 different cell lines. Compounds 2 and 8 proved to be the most active ones among the other target compounds. In a trial to investigate the mechanism of action of the target compounds, DNA binding activity was also investigated. Compounds 3f, 4-8 exhibited good binding activity explaining their mechanism. In addition, molecular modeling studies were also performed for more clearance of the data obtained from the biological screening.

New thiazolopyrimidine as anticancer agents: Synthesis, biological evaluation, DNA binding, molecular modeling and ADMET study.

In the present study, new series of thiazolopyrimidine derivatives was synthesized as purine analogs. The structures of the products were confirmed through spectroscopic techniques such as NMR and mass spectrometry. In addition, the synthesized compounds were evaluated as antitumor active agent through NCI screening protocol against 60 different cell lines under 9 different panels. Furthermore, DNA binding activity of the compounds was also evaluated. The results revealed that compound 35 proved to be the most active member of the tested series and it is promoted to the 5-dose testing where it gives GI50, TGI and LC50 values of 1.07, 6.61, 34.7 µM respectively. Furthermore, it also proved to have a good DNA binding activity with value that is comparable with that produced by doxorubicin which was used as positive standard. In addition, compound 27 was proved to be the most active DNA binding agent with binding affinity 28.38 ± 1.1. The pharmacokinetic properties were also calculated. Molecular docking studies suggested binding mode of compounds 27 and 35 to DNA minor groove via hydrogen bonding interaction. The anticancer activity of compounds 27 and 35 may be attributed to DNA binding.