Indole-containing compounds are widely distributed in the plant and animal kingdom, and their biological activity and pharmacological properties have prompted research into their chemical properties. This study developed a one-pot methodology for the synthesis of 3-aminoindole derivatives using copper- and ligand-free Sonogashira cross-coupling reaction conditions. The synthesised 3-aminoindole derivatives were confirmed using spectroscopic techniques. The resulting 3-aminoindole derivatives were biologically evaluated against Mycobacterium tuberculosis and Plasmodium falciparum. For example, indole derivatives 10a (7.813µM) and 10j (8.332µM) were the most active derivatives in the CAS and ADC media, respectively.

Background: Despite being considered a gold standard chemotherapeutic drug, cisplatin is associated with dose-limiting toxicity, especially nephrotoxicity. This highlights the need for safe and effective adjuvant agents that protect against cisplatin-induced toxicity without affecting its anticancer activity. This study investigated the potential of Momordica balsamina aqueous extract (MBAE) as an adjuvant to reduce cisplatin-induced kidney cell damage and death. Methods: The phytochemical analysis of the extract was done using Gas Chromatography-Mass Spectrometry. The effects of the extract in combination with cisplatin on cell viability in 2D and 3D cultures of HEK-293 and MDA-MB-231 cells were assessed using CCK-8, CellTiter-Glo 3D, and spheroid growth assays, respectively. Cell death in 2D HEK-293 and MDA-MB-231 cultures was assessed using Annexin V-FITC. DNA damage and cell cycle progression were analyzed using multicolor DNA damage and cell cycle analysis assays, respectively, while protein expression was determined by Western blotting in 2D HEK-293 cells. Results: A sum of 26 compounds, ranging from terpenoids, furans, steroids, flavanols and azaflavanols were tentatively identified. The combinatorial treatments increased HEK-293 viability in 2D and 3D cultures as well as enhanced spheroid diameter and growth. Comparatively, the co-treatment increased MDA-MB-231 cell viability in 2D models following treatment with 800 µg/ml at 24 h, while significantly reducing viability at 48 h. No notable changes in MDA-MB-231 spheroid diameters were observed although growth rate and spheroid viability decreased. The combinatory treatments increased early apoptotic cell death in a time-dependent manner in HEK-293 cells. On the other hand, a concentration- and time-dependent increase in late apoptotic cells percentages was observed in MDA-MB-231 cells. Cell cycle analysis revealed MBAE modulated the cell cycle by halting cells in the G0/G1-phase following treatment with 200 µg/ml while 800 ug/ml supplementation promoted cell cycling by shifting cell cycle arrest from the S-phase to the G2/M phase. Furthermore, a concentration-dependent decrease in pATM, pH2A.X, and co-activation was observed, although DNA damage worsened after 48 h of exposure. The combinatorial treatments modulated Bax/Bcl-2 ratios while upregulating p53, p21, and PARP1 protein expression to prioritize DNA repair over cell death. Conclusion: The data indicate that the extract has significant potential as a renoprotective agent in cisplatin therapy.