The biological rationale for targeting CDK1 is compelling. CDK1 is the master regulator of the G2-to-M transition in the cell cycle, the moment when a cell commits to dividing. Paired with cyclin B, it forms the M-phase promoting factor that phosphorylates the proteins responsible for chromosome condensation and spindle assembly. Unlike CDK2, CDK4, and CDK6, which show functional redundancy, CDK1 has no substitute at this checkpoint. Many tumors, particularly those carrying p53 mutations that cripple the G1 checkpoint, become dangerously dependent on CDK1 to enter mitosis even when DNA is damaged. Blocking CDK1 can therefore trigger mitotic catastrophe and apoptosis selectively in cancer cells, while normal cells with intact checkpoints pause and repair instead.

Despite this therapeutic logic, no CDK1 inhibitor has yet been approved by the FDA. Early pan-CDK inhibitors such as flavopiridel, now known as alvocidib, showed activity against leukemia and multiple myeloma but failed on selectivity, producing toxicity, diarrhea, nausea, and hepatotoxicity. Roniciclib trials in small-cell lung cancer were halted after severe adverse effects. Dinaciclib, which targets CDK1, CDK2, CDK5, and CDK9, remains the most clinically advanced agent, but the field continues to search for molecules with cleaner safety profiles. Natural products, which often carry lower intrinsic toxicity and can engage multiple pathways simultaneously, have emerged as an attractive hunting ground.

The research team turned to the NPACT database, a curated collection of plant-derived anticancer compounds, and focused on benzofuranoid phytochemicals from Morus alba. Rather than screening millions of synthetic molecules, they performed a targeted virtual screen of compounds with documented anticancer relevance. The CDK1 crystal structure, resolved at 2.33 angstroms and retrieved from the Protein Data Bank under the identifier 6GU6, was prepared in UCSF Chimera, and ligands were energy-minimized with the MMFF94 force field before docking with AutoDock Vina through the PyRx interface.

The docking results were striking. Mulberrofuran L bound CDK1 with a score of minus 8.5 kilocalories per mole, followed by mulberrofuran X at minus 8.2, mulberrofuran Y at minus 8.0, and euparin and 6-methoxy-tremetone at minus 7.7 each. Dinaciclib, the reference drug, scored only minus 6.6 kilocalories per mole. The docking protocol was validated by redocking the co-crystallized dinaciclib into the binding pocket, yielding a root-mean-square deviation of 1.38 angstroms, well below the 2-angstrom threshold that confirms a docking method reproduces known binding poses reliably.

Drug-likeness and pharmacokinetic filtering narrowed the field further. All five top compounds largely satisfied Lipinski’s Rule of Five, with the single exception of elevated lipophilicity: mulberrofuran L, X, and Y each showed logP values above 5, a violation the authors note may compromise aqueous solubility and oral bioavailability but does not automatically disqualify a compound. Predicted potency, estimated with the CODD-PRED server using machine learning models trained on curated bioactivity data, ranged from 5.28 to 5.48 in pIC50 terms, with mulberrofuran L scoring highest. The decisive filter was toxicity. ADMET profiling with the Deep-PK server flagged mulberrofuran Y, euparin, and 6-methoxy-tremetone for carcinogenicity and hepatotoxicity concerns, leaving mulberrofuran L and mulberrofuran X as the only candidates with clean toxicity profiles.

Those two survivors, along with dinaciclib as a benchmark, were then subjected to 200-nanosecond all-atom molecular dynamics simulations in GROMACS using the CHARMM36 force field. The mulberrofuran X complex proved the most stable of the three, showing the lowest and most consistent root-mean-square deviation at roughly 0.25 to 0.32 nanometers, the tightest radius of gyration at 2.32 to 2.36 nanometers, and the lowest solvent-accessible surface area, all signs of a compact, well-behaved protein-ligand complex. Mulberrofuran L fluctuated more, with RMSD values between 0.35 and 0.55 nanometers, though its excursions settled over time. Principal component analysis reinforced the picture: mulberrofuran X formed a tight conformational cluster, while mulberrofuran L sampled a broader range of motion along the first two principal components, and the free energy landscape confirmed that both compounds occupied well-defined low-energy minima rather than drifting into unstable states.

The energetic verdict was perhaps the study’s most eye-catching result. MM-GBSA binding free energy calculations, performed on frames extracted from the equilibrated trajectories, gave minus 15.66 kilocalories per mole for mulberrofuran X and minus 11.82 for mulberrofuran L, compared with just minus 2.31 for dinaciclib. Since more negative values indicate stronger binding, both mulberry compounds appeared to outperform the clinical reference by a wide margin in this metric. Density functional theory calculations added an electronic dimension: dinaciclib showed the smallest HOMO-LUMO gap at 2.894 electron volts, indicating the highest chemical softness and reactivity, while mulberrofuran L, at 2.943 electron volts, sat close behind, and mulberrofuran X, at 3.832 electron volts, was the most electronically stable of the three.

The authors are careful to frame these findings as hypothesis-generating rather than proof of therapeutic value. Every result in the study is computational, and the pipeline’s predictions, from pIC50 estimates to CYP450 inhibition flags for the mulberrofuran compounds, all require experimental confirmation. The team recommends in vitro kinase inhibition assays and cell viability tests such as MTT or CCK-8 to verify that mulberrofuran L and X actually suppress CDK1 in living cells, followed by cytotoxicity, selectivity, and mechanistic studies in cancer cell lines and eventually animal models. Predicted CYP inhibition in particular raises potential drug-drug interaction risks that only dedicated laboratory pharmacokinetics can resolve.

Even with those caveats, the study adds mulberry phytochemicals to a growing list of plant-derived CDK modulators, joining curcumin, wogonin, honokiol, and atractylenolide I, all of which have shown cell cycle arrest effects in preclinical cancer models. What distinguishes this work is the depth of the computational validation: a multi-level workflow spanning docking, dynamics, free energy, and quantum chemistry that converged on the same two candidates from different angles. If laboratory experiments bear out the simulations, the humble mulberry, a tree better known for feeding silkworms than fighting tumors, could yield lead structures for a class of cancer drugs that has long eluded medicinal chemists: selective, tolerable inhibitors of CDK1.

Subject of Research: Computational screening of Morus alba phytochemicals as CDK1 inhibitors for cancer therapy

Article Title: In silico investigation of mulberry phytochemicals targeting CDK1 in cancer using molecular docking and computational approaches

Article References: Abdullah, S., Nisar, S., Irshad, M., Saini, R. S., Alam, M., Ansari, I., & Junaid, M. (2026). In silico investigation of mulberry phytochemicals targeting CDK1 in cancer using molecular docking and computational approaches. Discover Chemistry, 3(1), Article 562. https://doi.org/10.1007/s44371-026-01020-w

Image Credits: AI Generated

DOI: 10.1007/s44371-026-01020-w

Keywords: CDK1, Morus alba, molecular docking, molecular dynamics simulation, phytochemicals, cancer, drug discovery, MM-GBSA, ADMET, DFT, mulberrofuran, cell cycle

The environmental stakes are considerable. Rhodamine B carries a xanthene ring system substituted with two di-ethylamino groups and a carboxyphenyl group, and it ranks among the more problematic dye pollutants in aquatic systems. Conventional wastewater treatments exist, but photocatalytic degradation powered by abundant, clean solar energy has emerged as a green, pollution-free and comparatively inexpensive alternative. What makes the new work distinctive is not just the catalyst itself but the way it is made: instead of preparing the porphyrin-semiconductor composite in advance, purifying it, drying it and storing it, the team simply mixed the two components into the dye solution and let weak physical interactions assemble the composite on the spot.

That in-situ strategy, the authors argue, sidesteps the energy inputs and extra solvent consumption that ex-situ composite fabrication demands. It also avoids the shelf-life problem: pre-made composites can degrade over time through moisture, heat, contamination or self-degradation. The trade-off, which the researchers candidly acknowledge, is that the components are not strongly bonded to each other, since P1 lacks strong anchoring groups, and much of the catalyst was lost through the filter paper during recovery after the first photocatalytic cycle. They propose functionalizing the porphyrin with carboxylic acid anchoring groups or inducing self-assembly on the ZnO surface as future fixes.

Every step of the synthesis was designed with sustainability in mind. The porphyrin was made by an acid-catalyzed condensation of pyrrole and 4-methoxybenzaldehyde in a water-methanol mixture at room temperature, using just 10 milliliters of hydrochloric acid rather than the large quantities of harsher catalysts and chlorinated solvents that traditional Adler-type methods require. A single modification to the published procedure proved decisive: instead of stirring the DMF solution overnight after reflux, the team left it undisturbed. That small change yielded well-separated, lozenge-shaped violet crystals of high quality, suitable for single-crystal X-ray diffraction, while avoiding the mechanical disturbance that disrupts molecular ordering during crystal growth and cutting the energy cost of overnight stirring.

The crystallography revealed a monoclinic P21/c structure with an asymmetric unit containing half the molecule, bifurcated hydrogen bonds within the porphyrin core, and a three-dimensional supramolecular framework stitched together by non-covalent C-H···π interactions. The crystallinity matters for catalysis: ordered porphyrin nanocrystals favor enhanced electron transport and photostability, so the crystalline P1 is expected to outperform amorphous forms of the same molecule.

The zinc oxide nanoparticles were equally green in their origins. Fresh Morus alba leaves, collected on the college campus in April, were steeped in distilled water at 70 degrees Celsius for half an hour, releasing phytochemicals such as alkaloids, phenols and flavonoids into solution. When this extract was added to zinc sulfate under alkaline conditions and stirred at 45 degrees Celsius, the biomolecules reduced zinc ions to metallic zinc, which reacted with dissolved oxygen to form ZnO nuclei, while other phytochemicals capped the growing particles and kept them from clumping. Notably, the team skipped the energy-intensive calcination step that most green syntheses employ, arguing that high-temperature treatment often fails to remove organic impurities anyway and promotes agglomeration that enlarges the particles and shrinks their surface area.

Skipping calcination did not compromise quality. Powder X-ray diffraction confirmed a phase-pure hexagonal wurtzite structure matching the standard reference card, with an average crystallite size of about 20 nanometers, smaller than typically reported for calcinated green-synthesized ZnO. Scanning electron microscopy showed flower-like agglomerates and, at higher magnification, the hexagonal prisms characteristic of wurtzite crystals. Energy-dispersive X-ray spectroscopy detected only zinc, oxygen and carbon, the latter attributable to the sample grid and residual capping phytochemicals, with no foreign elements such as potassium, calcium or sodium that often contaminate calcinated phytosynthesized samples. Zinc and oxygen accounted for 56.48 and 23.15 weight percent respectively. Optical measurements placed the ZnO band gap at 3.5 electronvolts, with the characteristic absorption peak at 350 nanometers confirming nano-scale rather than bulk particles, while the porphyrin’s sharp Soret band at 418 nanometers corresponded to a 2.9 electronvolt gap.

The photocatalytic tests were conducted outdoors under real subtropical sunlight in Delhi between late April and early May, during the pre-monsoon peak of solar intensity. Dye solutions of 10 micromolar rhodamine B were monitored by the decay of the absorption peak near 550 nanometers. As irradiation proceeded, the peak intensity fell and shifted toward shorter wavelengths, a signature of stepwise de-ethylation: reactive oxygen species strip the N-ethyl groups one by one, reducing electron density on the conjugated chromophore with each removal. The solutions faded progressively but did not turn completely colorless, indicating that the central xanthene ring largely survived under these conditions even as the ethyl groups were stripped away.

The performance hierarchy was clear. Porphyrin alone managed 50.87 percent degradation, hampered by fast recombination of its photoinduced electron-hole pairs. Bare ZnO nanoparticles reached 67.42 percent, benefiting from their large surface area and abundant reactive sites. The ZnO@P1 composite led at 76.12 percent, 1.13 times better than ZnO and 1.5 times better than P1. Pseudo-first-order kinetic analysis gave rate constants of 5.93 x 10-3 per minute for P1, 9.36 x 10-3 for ZnO and 1.20 x 10-2 for the composite. The mechanism behind the synergy is a classic heterojunction story: the lower-band-gap porphyrin absorbs visible photons, and its excited electrons migrate to the conduction band of the higher-band-gap ZnO while holes flow the opposite way, achieving spatial separation of charge carriers. With recombination suppressed, more electrons and holes survive to react with water and oxygen, generating the hydroxyl radicals and superoxide anion radicals that actually dismantle the dye molecules toward carbon dioxide and water.

Compared with published ZnO-porphyrin composites, the new system looks modest at first glance. Cardanol-based H2Pp-ZnO and CuPp-ZnO composites degraded 98 percent of rhodamine B in 30 minutes under tropical sunlight, a ZnO/TAPPI-CoTPPS system achieved complete degradation in 120 minutes under simulated light, and a ZnO/TCPP composite reached 97 percent in 180 minutes. But the dosage comparison changes the picture: the Delhi composite ran at 0.1 grams per liter, roughly ten times less catalyst than the cardanol systems and twenty times less than the TAPPI-CoTPPS system for the same dye concentration, and it did so under natural rather than simulated illumination, where passing clouds can interrupt the light supply. The authors suggest the composite could achieve further degradation with extended irradiation. As a proof of concept for on-demand, low-energy composite formation from plant-derived nanomaterials and green-synthesized porphyrins, the work points toward a future where wastewater treatment catalysts are grown, not manufactured, and assembled exactly when and where they are needed.

Subject of Research: Green synthesis of a ZnO-porphyrin composite for solar-light photocatalytic degradation of rhodamine B dye in water

Article Title: Eco-friendly ZnO nanoparticles coupled with porphyrin for enhanced solar light driven degradation of rhodamine B

Article References: Anushikha, & Dechan, P. (2026). Eco-friendly ZnO nanoparticles coupled with porphyrin for enhanced solar light driven degradation of rhodamine B. Results in Chemistry, 31, Article 103903. https://doi.org/10.1016/j.rechem.2026.103903

Image Credits: AI Generated

DOI: 10.1016/j.rechem.2026.103903

Keywords: zinc oxide nanoparticles, porphyrin, photocatalysis, rhodamine B, green synthesis, Morus alba, solar light, dye degradation, wastewater treatment, heterojunction, reactive oxygen species, sustainable chemistry