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Synthesis, antimicrobial evaluation, and QSAR analysis of 2-isopropyl-5-methylcyclohexanol derivatives

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Abstract

A series of 2-isopropyl-5-methylcyclohexanol derivatives were synthesized and evaluated for their antibacterial activity against Gram-positive Staphylococcus aureus and Bacillus subtilis and Gram-negative Escherichia coli and in vitro antifungal activity against Candida albicans and Aspergillus niger. The results of antimicrobial activity demonstrated that the compounds 10, 20, and 21 were the most active ones among the synthesized compounds. The QSAR studies revealed the importance of dipole moment (μ), total energy (Te), and topological parameters (κ1 and κ3) in describing the antimicrobial activity of 2-isopropyl-5-methylcyclohexanol derivatives.

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References

  • Bajaj S, Sambi SS, Madan AK (2005) Prediction of anti-inflammatory activity of N-arylanthranilic acids: computational approach using refined Zagreb indices. Croat Chem Acta 78(2):165–174

    CAS  Google Scholar 

  • Balaban AT (1982) Discriminating distance based topological indices. Chem Phys Lett 89:399–404

    Article  CAS  Google Scholar 

  • Beck B, Bidaux G, Bavencoffe A, Lemonnier L, Thebault S, Shuba Y, Barrit G, Skryma R, Prevarskaya N (2007) Prospects for prostate cancer imaging and therapy using high-affinity TRPM8 activators. Cell Calcium 41:285–294

    Article  PubMed  CAS  Google Scholar 

  • Dambolena JS, Lopez AG, Canepa MC, Theumer MG, Zygadlo JA, Rubinstein HR (2008) Inhibitory effect of cyclic terpenes (limonene, menthol, menthone and thymol) on Fusarium verticillioides MRC 826 growth and fumonisin B1 biosynthesis. Toxicon 51(1):37–44

    Article  PubMed  CAS  Google Scholar 

  • Desousa DP, Raphael E, Brocksom U, Brocksom TJ (2007) Sedative effect of monoterpene alcohols in mice: a preliminary screening. Z Nat 62(7/8):563–566

    Google Scholar 

  • Emami S, Foroumadi A, Falahati M, Loffali E, Rajabalian S, Ebrahimi SA, Farahyar S, Shafiee A (2008) 2-Hydroxy phenacyl azoles and related azolium derivative as antifungal agents. Bioorg Med Chem Lett 18:141–146

    Article  PubMed  CAS  Google Scholar 

  • Galeotti N, Mannelli LDC, Mazzanti G, Bartolini A, Ghelardini C (2002) Menthol: a natural analgesic compound. Neurosci Lett 322:145–148

    Article  PubMed  CAS  Google Scholar 

  • Garcia DA, Bujons J, Vale C, Sunol C (2006) Allosteric positive interaction of thymol with the GABA-A receptor in primary cultures of mouse cortical neurons. Neuropharmacology 50:25–35

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Domenech R, Rios-Santamariana I, Catala A, Calabuig C, Castillo LD, Galvez J (2003) Application of molecular topology to the prediction of antifungal activity for a set of dication-substituted carbazoles, furans and benzimidazoles. J Mol Str (Theochem) 624:97–107

    Article  CAS  Google Scholar 

  • Golbraikh A, Tropsha A (2002) Beware of q 2!. J Mol Graph Model 20(4):269–276

    Article  PubMed  CAS  Google Scholar 

  • Haeseler G, Maue D, Grosskreutz J, Bufler J, Nentwig B, Piepenbrock S, Dengler R, Leuwer M (2002) Voltage-dependent block of neuronal and skeletal muscle sodium channels by thymol and menthol. Eur J Anaesth 19:571–579

    CAS  Google Scholar 

  • Hansch C, Fujita T (1964) p-σ-π Analysis. A method for the correlation of biological activity and chemical structure. J Am Chem Soc 86:1616–1626

    Article  CAS  Google Scholar 

  • Hansch C, Leo A, Unger SH, Kim KH, Nikaitani D, Lien EJ (1973) Aromatic substituent constants for structure-activity correlations. J Med Chem 16:1207–1216

    Article  PubMed  CAS  Google Scholar 

  • Hatya SA, Aki-sener E, Tekiner-Gulbas B, Yildiz I, Temiz-Arpaci O, Yalcin I, Altanlar N (2006) Synthesis, antimicrobial activity and QSARs of new benzoxazine-3-ones. Eur J Med Chem 41:1398–1404

    Article  Google Scholar 

  • Hawthorn M, Ferrante J, Luchowski E, Rutledge A, Wei XY, Triggle DJ (1988) The actions of peppermint oil and menthol on calcium channel dependent processes in intestinal, neuronal and cardiac preparations. Aliment Pharmacol Therap 2:101–118

    Article  CAS  Google Scholar 

  • Heravi JM, Kyani A (2005) A use of computer-assisted methods for the modeling of the retention time of a variety of volatile organic compounds: a PCA-MLR-ANN approach. J Chem Inf Comput Sci 44:1328–1335

    Google Scholar 

  • Janbaz KH, Gilani AH (2002) Menthol prevents liver damage induced by paracetamol and CCl4. Pak J Biol Sci 5(10):1101–1103

    Article  Google Scholar 

  • Juergens UR, Stober M, Vetter H (1998) The anti-inflammatory activity of L-menthol compared to mint oil in human monocytes in vitro: a novel perspective for its therapeutic use in inflammatory diseases. Eur J Med Res 3(12):539–545

    PubMed  CAS  Google Scholar 

  • Karelson M, Lobanov VS, Katritzky AR (1996) Quantum—chemical descriptors in QSAR/QSPR studies. Chem Rev 96(3):1027–1043

    Article  PubMed  CAS  Google Scholar 

  • Kier LB, Hall LH (1976) Molecular connectivity in chemistry and drug research. Academic Press, New York, pp 79–82

    Google Scholar 

  • Kim HK, Yun YK, Ahn YJ (2008) Fumigant toxicity of cassia bark and cassia and cinnamon oil compounds to dermatophagoides farinae and dermatophagoides pteronyssinus (Acari: Pyroglyphidae). Exp Appl Acarol 44(1):1–9

    Article  PubMed  CAS  Google Scholar 

  • Kotan R, Kordali S, Cakir A (2007) Screening of antibacterial activities of twenty-one oxygenated monoterpenes. Z Nat C 62(7/8):507–513

    CAS  Google Scholar 

  • Kumar A, Sharma P, Gurram VK, Rane N (2006) Studies on synthesis and evaluation of quantitative structure–activity relationship of 10-methyl-6-oxo-5-arylazo-6, 7-dihydro-5H-[1,3]azaphospholo[1,5-d][1,4]benzodiazepin-2-phospha-3-ethoxycarbonyl-1-phosphorus dichlorides. Bioorg Med Chem Lett 16:2484–2491

    Article  PubMed  CAS  Google Scholar 

  • Kumar A, Narasimhan B, Kumar D (2007) Synthesis, antimicrobial and QSAR studies of substituted benzamides. Bioorg Med Chem 15:4113–4124

    Article  PubMed  CAS  Google Scholar 

  • Macpherson LJ, Hwang SW, Miyamoto T, Dubin AE, Patapoutian A, Story GM (2006) More than cool: promiscuous relationships of menthol and other sensory compounds. Mol Cell Neurosci 32:335–343

    Article  PubMed  CAS  Google Scholar 

  • Mimica-Dukic N, Bozin B, Sokovic M, Mihajlovic B, Matavulj M (2003) Antimicrobial and antioxidant activities of three Mentha species essential oils. Planta Med 69(5):413–419

    Article  PubMed  CAS  Google Scholar 

  • Miyazawa M, Watanabe H, Kameoka H (1997) Inhibition of acetylcholinesterase activity by monoterpenoids with a p-menthane skeleton. J Agric Food Chem 45:677–679

    Article  CAS  Google Scholar 

  • Narasimhan B, Kothwade UR, Pharande DS, Mourya VK, Dhake AS (2003) Syntheses and QSAR studies of sorbic, cinnamic and ricinoleic acid derivatives as potential antibacterial agents. Indian J Chem 42(B):2828–2834

    Google Scholar 

  • Narasimhan B, Belsare D, Pharnde P, Mourya V, Dhake AS (2004) Esters, amides and substituted derivatives of cinnamic acid: synthesis, antimicrobial activity and QSAR investigations. Eur J Med Chem 39(10):827–834

    Article  PubMed  CAS  Google Scholar 

  • Narasimhan B, Kumari M, Dhake AS, Sundaravelan C (2006a) QSAR studies on structurally similar 2-arylidene-4-(4-phenoxy-phenyl) but-3-en-4-olides as anti-inflammatory agents. Arkivoc xiii:73–82

    Google Scholar 

  • Narasimhan B, Mourya VK, Dhake AS (2006b) Design, synthesis, antibacterial and QSAR studies of myristic acid derivatives. Bioorg Med Chem Lett 16:3023–3029

    Article  PubMed  CAS  Google Scholar 

  • Narasimhan B, Kumari M, Jain N, Dhake AS, Sundaravelan C (2006c) Correlation of antibacterial activity of some n-[5-(2-furanyl)-2-methyl-4-oxo-4h-thieno[2,3-d]pyrimidin-3-yl]-carboxamide and 3-substituted-5-(2-furanyl)-2-methyl-3h-thieno[2,3-d]pyrimidin4-ones with topological indices using Hansch analysis. Bioorg Med Chem Lett 16:4951–4958

    Article  PubMed  CAS  Google Scholar 

  • Narasimhan B, Narang R, Judge V, Ohlan S, Ohlan R (2007a) Synthesis, antimicrobial and QSAR studies of substituted anilides. ARKIVOC xv:112–126

    Google Scholar 

  • Narasimhan B, Judge V, Narang R, Ohlan S, Ohlan R (2007b) Quantitative structure–activity relationship studies for prediction of antimicrobial activity of synthesized 2,4-hexadienoic acid derivatives. Bioorg Med Chem Lett 17:5836–5845

    Article  PubMed  CAS  Google Scholar 

  • Narasimhan B, Mourya VK, Dhake AS (2007c) QSAR studies of antibacterial ricinoleic acid derivatives. Pharm Chem J 41(3):133–139

    Article  CAS  Google Scholar 

  • Ohlan R, Ohlan S, Judge V, Narang R, Ahuja M, Narasimhan B (2007) 2-(2,4-Difluorophenyl)-1,3-bis(1,2,4-triazol-1-yl)propan-2-ol derivatives: synthesis, antifungal evaluation and QSAR studies by Hansch analysis. ARKIVOC xiv:172–184

    Google Scholar 

  • Pharmacopoeia of India (1996) Ministry of Health Department, Govt. of India, New Delhi, vol II, A-88

  • Pillai AD, Rani S, Rathod PD, Xavier FP, Vasu KK, Padh H, Sudarsanam V (2005) QSAR studies on some thiophene analogs as anti-inflammatory agents: enhancement of activity by electronic parameters and its utilization for chemical lead optimization. Bioorg Med Chem 13:1275–1283

    Article  PubMed  CAS  Google Scholar 

  • Randic M (1975) On the characterization of molecular branching. J Am Chem Soc 97:6609–6615

    Article  CAS  Google Scholar 

  • Randic M (1993) Comparative regression analysis. Regressions based on single descriptor. Croat Chem Acta 66:289–312

    CAS  Google Scholar 

  • Schaper KJ (1999) Free-Wilson-type analysis of non-additive substituent effects on THPB dopamine receptor affinity using artificial neural networks. Quant Struct Act Relat 18:354–360

    Article  CAS  Google Scholar 

  • Schelz Z, Molnar J, Hohmann J (2006) Antimicrobial and antiplasmid activities of essential oils. Fitoterapia 77:279–285

    Article  PubMed  CAS  Google Scholar 

  • Shadomy S, Espinel A (1980) Manual of clinical microbiology. American Society for Microbiology, Washington, DC, 647 pp

  • Sharma P, Rane N, Gurram VK (2004) Synthesis and QSAR studies of pyrimido[4,5-d]pyrimidine-2,5-dione derivatives as potential antimicrobial agents. Bioorg Med Chem Lett 14:4185–4190

    Article  PubMed  CAS  Google Scholar 

  • Sharma P, Kumar A, Sharma M (2006) Synthesis and QSAR studies on 5-[2-(2-methylprop1-enyl)-1H-benzimidazol-1yl]-4,6-diphenyl-pyrimidin-2-(5H)-thione derivatives as antibacterial agents. Eur J Med Chem 41:833–840

    Article  PubMed  CAS  Google Scholar 

  • Sidell N, Taga T, Hirano T, Kishimoto T, Saxom A (1991) Retinoic acid-induced growth inhibition of a human myeloma cell line via down-regulation of IL-6 receptors. J Immunol 146(11):3809–3814

    PubMed  CAS  Google Scholar 

  • Silva MIG, Neto MR, Neto PFT, Moura BA, Amaral JF, Desousa DP, Vasconcelos SMM, Desousa FCF (2007) Central nervous system activity of acute administration of isopulegol in mice. Pharmacol Biochem Behav 88(2):141–147

    Article  PubMed  CAS  Google Scholar 

  • Sortino M, Delgado P, Jaurez S, Quiroga J, Abonia R, Insuasey B, Nogueras M, Rodero L, Garibotto FM, Enriz RD, Zacchino SA (2007) Synthesis and antifungal activity of (Z)-5-arylidenerhodanines. Bioorg Med Chem Lett 15:484–494

    Article  CAS  Google Scholar 

  • SPSS Inc. (1999) SPSS for Windows, Version 10.05. SPSS Inc., Bangalore

  • Tamaoki J, Chiyotani A, Sakai A, Takemura H, Konno K (1995) Effect of menthol vapour on airway hyperresponsiveness in patients with mild asthma. Respir Med 89(7):503–504

    Article  PubMed  CAS  Google Scholar 

  • Tetko IV, Tanchuk VY, Villa AE (2001) Prediction of n-octanol/water partition coefficients from PHYSPROP database using artificial neural networks and E-state indices. J Chem Inf Comput Sci 41:1407–1421

    Article  PubMed  CAS  Google Scholar 

  • Trombetta D, Castelli F, Sarpietro MG, Venuti V, Cristini M, Daniele C, Sajja A, Mazzanti G, Bisigano G (2005) Mechanisms of antibacterial action of three monoterpenes. Antimicrob Agents Chemother 49(6):2474–2478

    Article  PubMed  CAS  Google Scholar 

  • TSAR (2000) TSAR 3D version 3.3. Oxford Molecular Limited

  • Vasanthanthan P, Lakshmi M, Babu MA, Gupta AK, Koshedikar SG (2006) QSAR study of 3-phenyl-5-acyloxymethyl-2H,5H-furan-2-ones as antifungal agents: the dominant role of electronic parameter. Chem Pharm Bull 54:583–587

    Article  Google Scholar 

  • Wang XH, Tang Y, Xie Q, Qiu Z (2006) QSAR study of 4-phenylpiperidine derivatives as μ opioid agonists by neural network method. Eur J Med Chem 41:226–232

    Article  PubMed  CAS  Google Scholar 

  • Wiener H (1947) Structural determination of paraffin boiling points. J Am Chem Soc 69:17–20

    Article  PubMed  CAS  Google Scholar 

  • Yao XJ, Panye JP, Doucet JP, Zang RS, Chen HF, Lice MC, Hu ZD, Fan BT, Liu MC, Hu ZD (2004) Comparative study of QSAR/QSPR correlations using support vector machines, radial basis function neural networks, and multiple linear regression. J Chem Inf Comput Sci 44:1257–1266

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Guru Jambheswar University of Science and Technology, Hisar, 125001, India

    Manjeet Singh, Sunil Kumar & Ashwani Kumar

  2. Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001, India

    Pradeep Kumar & Balasubramanian Narasimhan

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  1. Manjeet Singh
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  2. Sunil Kumar
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  3. Ashwani Kumar
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  5. Balasubramanian Narasimhan
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Correspondence to Balasubramanian Narasimhan.

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Singh, M., Kumar, S., Kumar, A. et al. Synthesis, antimicrobial evaluation, and QSAR analysis of 2-isopropyl-5-methylcyclohexanol derivatives. Med Chem Res 21, 511–522 (2012). https://doi.org/10.1007/s00044-011-9550-3

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